We hypothesize that sPLA(2)IIa modulates lung cancer cell growth in K-ras mutant cells and that sPLA(2)IIa expression in human lung tumors is increased in K-ras mutant tumors.
Methods: Baseline sPLA(2)IIa expression in K-ras mutant lung cancer cell lines (A549, SW1573, H358, H2009) was assessed. Cells were treated with a specific sPLA(2)IIa inhibitor and evaluated for apoptosis and cell viability. Nuclear factor kappa-b (NF-kappa B)
and extracellular signal-regulated kinase 1/2 activity were detected by Western blot. Human tumor samples were evaluated for sPLA(2)IIa mRNA expression by quantitative find more reverse-transcription polymerase chain reaction.
Results: Cytotoxicity of sPLA(2)IIa inhibition correlates https://www.selleckchem.com/products/pu-h71.html with sPLA(2)IIa expression. Apoptosis in response to sPLA(2) inhibition parallels attenuation in NF-kappa B activity. In addition, sPLA(2)IIa expression in human tumors correlates with squamous cell pathology and increasing stage of K-ras mutant lung tumors.
Conclusions: Baseline sPLA(2)IIa expression predicts response to sPLA(2)IIa inhibition in some K-ras mutant lung cancer cells. This finding is independent of p53 mutation status. Furthermore, squamous tumors and advanced-stage K-ras mutant tumors express more sPLA(2)IIa.
These data support a role for sPLA(2)IIa as a potential global therapeutic target in the treatment of lung cancer. (J Thorac Cardiovasc Surg 2012;144:1479-85)”
“Meganucleases (MNs) are highly specific enzymes that can induce homologous over recombination in different types of cells, including mammalian cells. Consequently, these enzymes are used as scaffolds for the development of custom gene-targeting tools for gene therapy or cell-line development. Over the past 15 years, the high resolution X-ray structures of several MNs from the LAGLIDADG family have improved our understanding of their protein-DNA interaction and mechanism of DNA cleavage. By developing and utilizing high-throughput screening methods to test a large number of variant-target combinations, we have been able to re-engineer scores of I-CreI
derivatives into custom enzymes that target a specific DNA sequence of interest. Such customized MNs, along with wild-type ones, have allowed for exploring a large range of biotechnological applications, including protein-expression cell-line development, genetically modified plants and animals and therapeutic applications such as targeted gene therapy as well as a novel class of antivirals.”
“Translational approaches to study the neural substrates of stress and assess the mechanistic efficacy of novel anti-anxiety agents necessitate the use of stressors with a similar degree of saliency across species. The alpha-2 adrenoreceptor antagonist yohimbine represents an attractive experimental tool owing to its well-documented stress-inducing properties in humans and laboratory species.
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