4 resultados para inhibitor design
em Deakin Research Online - Australia
Resumo:
Electrochemical methods can be used more effectively if innovative experiments are designed and employed. This is especially true if a corrosion system to be tested involves inhibitors that could change the mechanism and pattern of corrosion in complex ways. This paper discusses corrosion inhibitor test design using several practical cases as examples. Particular attention is on difficult issues such as the simulation of localized corrosion phenomena and the influence of corrosion mechanism on inhibitor test results. ©2012 by NACE International.
Resumo:
The use of corrosion inhibitors is a flexible and economical option for localised corro-sion control. Unfortunately some high performance traditional inhibitors are toxic or environmentally unacceptable. Various new approaches of designing environmentally friendly “greener” inhibitors have been reported in the literature; however the perfor-mance of inhibitors in preventing localised forms of corrosion are often not sufficiently evaluated. An obstacle in new inhibitor evaluation is technological difficulties associ-ated with the assessment of localised corrosion. It is a challenging task to design effective experiments that are able to assess not only the tendency, but also the rates and the distribution of localised corrosion. This paper provides an overview of some recent progress in methodologies for evaluating localised corrosion inhibitors.
Resumo:
Purpose:
Experimental Design:
Genes characteristic of the Hh MB subgroup were identified through published bioinformatic analyses. Thirty-two genes shown to be differentially expressed in fresh frozen and formalin-fixed paraffin-embedded tumor samples and reproducibly analyzed by RT-PCR were measured in matched samples. These data formed the basis for building a multi-gene logistic regression model derived through elastic net methods from which the five-gene Hh signature emerged after multiple iterations. Based on signature gene expression levels, the model computed a propensity score to determine Hh activation using a threshold set a priori. The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.
Results:
Five differentially expressed genes in MB (GLI1, SPHK1, SHROOM2, PDLIM3, and OTX2) were found to associate with Hh pathway activation status. In an independent validation study, Hh activation status of 25 MB samples showed 100% concordance between the five-gene signature and Affymetrix profiling. Further, in MB samples from 50 patients treated with sonidegib, all six patients who responded were found to have Hh-activated tumors. Three patients with Hh-activated tumors had stable or progressive disease. No patients with Hh-nonactivated tumors responded.
Conclusions:
This five-gene Hh signature can robustly identify Hh-activated MB and may be used to preselect patients who might benefit from sonidegib treatment.
Resumo:
PURPOSE: Malignant rhabdoid tumor (MRT) and atypical teratoid rhabdoid tumors (ATRT) are rare aggressive undifferentiated tumors primarily affecting the kidney and CNS of infants and young children. MRT are almost exclusively characterized by homozygous deletion or inactivation of the chromatin remodeling gene SMARCB1 SMARCB1 protein loss leads to direct impairment of chromatin remodeling and we have previously reported a role for this protein in histone acetylation. This provided the rationale for investigating the therapeutic potential of histone deactylase inhibitors (HDACi) in MRT. EXPERIMENTAL DESIGN: Whereas previously HDACis have been used at doses and schedules that induce cytotoxicity, in the current studies we have tested the hypothesis, both in vitro and in vivo, that sustained treatment of human MRT with low-dose HDACi can lead to sustained cell growth arrest and differentiation. RESULTS: Sustained low-dose panobinostat (LBH589) treatment led to changes in cellular morphology associated with a marked increase in the induction of neural, renal, and osteoblast differentiation pathways. Genome-wide transcriptional profiling highlighted differential gene expression supporting multilineage differentiation. Using mouse xenograft models, sustained low-dose LBH589 treatment caused tumor growth arrest associated with tumor calcification detectable by X-ray imaging. Histological analysis of LBH589-treated tumors revealed significant regions of ossification, confirmed by Alizarin Red staining. Immunohistochemical analysis showed increased TUJ1 and PAX2 staining suggestive of neuronal and renal differentiation, respectively. CONCLUSIONS: Low-dose HDACi treatment can terminally differentiate MRT tumor cells and reduce their ability to self-renew. The use of low-dose HDACi as a novel therapeutic approach warrants further investigation.
