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1.  Alterations in Genes of the EGFR Signaling Pathway and Their Relationship to EGFR Tyrosine Kinase Inhibitor Sensitivity in Lung Cancer Cell Lines 
PLoS ONE  2009;4(2):e4576.
Background
Deregulation of EGFR signaling is common in non-small cell lung cancers (NSCLC) and this finding led to the development of tyrosine kinase inhibitors (TKIs) that are highly effective in a subset of NSCLC. Mutations of EGFR (mEGFR) and copy number gains (CNGs) of EGFR (gEGFR) and HER2 (gHER2) have been reported to predict for TKI response. Mutations in KRAS (mKRAS) are associated with primary resistance to TKIs.
Methodology/Principal Findings
We investigated the relationship between mutations, CNGs and response to TKIs in a large panel of NSCLC cell lines. Genes studied were EGFR, HER2, HER3 HER4, KRAS, BRAF and PIK3CA. Mutations were detected by sequencing, while CNGs were determined by quantitative PCR (qPCR), fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH). IC50 values for the TKIs gefitinib (Iressa) and erlotinib (Tarceva) were determined by MTS assay. For any of the seven genes tested, mutations (39/77, 50.6%), copy number gains (50/77, 64.9%) or either (65/77, 84.4%) were frequent in NSCLC lines. Mutations of EGFR (13%) and KRAS (24.7%) were frequent, while they were less frequent for the other genes. The three techniques for determining CNG were well correlated, and qPCR data were used for further analyses. CNGs were relatively frequent for EGFR and KRAS in adenocarcinomas. While mutations were largely mutually exclusive, CNGs were not. EGFR and KRAS mutant lines frequently demonstrated mutant allele specific imbalance i.e. the mutant form was usually in great excess compared to the wild type form. On a molar basis, sensitivity to gefitinib and erlotinib were highly correlated. Multivariate analyses led to the following results:
 1. mEGFR and gEGFR and gHER2 were independent factors related to gefitinib sensitivity, in descending order of importance.
 2. mKRAS was associated with increased in vitro resistance to gefitinib.
Conclusions/Significance
Our in vitro studies confirm and extend clinical observations and demonstrate the relative importance of both EGFR mutations and CNGs and HER2 CNGs in the sensitivity to TKIs.
doi:10.1371/journal.pone.0004576
PMCID: PMC2642732  PMID: 19238210
2.  Highly mesoporous metal–organic framework assembled in a switchable solvent 
Nature Communications  2014;5:4465.
The mesoporous metal–organic frameworks are a family of materials that have pore sizes ranging from 2 to 50 nm, which have shown promising applications in catalysis, adsorption, chemical sensing and so on. The preparation of mesoporous metal–organic frameworks usually needs the supramolecular or cooperative template strategy. Here we report the template-free assembly of mesoporous metal–organic frameworks by using CO2-expanded liquids as switchable solvents. The mesocellular metal–organic frameworks with large mesopores (13–23 nm) are formed, and their porosity properties can be easily adjusted by controlling CO2 pressure. Moreover, the use of CO2 can accelerate the reaction for metal–organic framework formation from metal salt and organic linker due to the viscosity-lowering effect of CO2, and the product can be recovered through CO2 extraction. The as-synthesized mesocellular metal–organic frameworks are highly active in catalysing the aerobic oxidation of benzylic alcohols under mild temperature at atmospheric pressure.
Large pore metal–organic frameworks may have improved catalytic or molecular sieving properties. Here, the authors demonstrate that carbon dioxide expanded liquids can be used to synthesize these materials and that pore size may, to an extent, be tuned by varying gas pressure.
doi:10.1038/ncomms5465
PMCID: PMC4109014  PMID: 25047059

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