Plausible role of estrogens in pathogenesis, progression and therapy of lung cancer

Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor genep53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlation between hormone replacement therapy (HRT) or oral contraceptives (OCs), and increased mortality rates due to the increased incidence of malignant tumors, including lung cancer. Interestingly, two types of estrogen receptors have been detected in lung cancer cells: ERα and ERβ. The presence of ERα has been detected in tissues and non-small-cell lung carcinoma (NSCLC) cell lines. In contrast, overexpression of ERβ is a prognostic marker in NSCLC. Herein, we summarize the current knowledge on the role of estrogens in the etiopathogenesis of lung cancer, as well as biological, hormonal and genetic sex-related differences in this neoplasm

Prediction of Chromatographic Elution Order of Analytical Mixtures Based on Quantitative Structure-Retention Relationships and Multi-Objective Optimization

10.3390/molecules25133085Molecules2513308

Computer-assisted optimization of reversed-phase HPLC isocratic separations of neutral compounds

Rational selection of optimized exptl. conditions for chromatog. sepn. of analytes is realized nowadays by means of specialized computer programs. Two such programs, DryLab (LC Resources, Walnut Creek, California, USA) and ChromSword (Merck KGaA, Darmstadt, Germany), were compared. The aim of the study was to compare the optimization of chromatog. sepns. of neutral compds. performed isocratically in reversed-phase high performance liq. chromatog. (HPLC) systems. A detailed description and discussion of the differences in predicted and exptl. chromatog. retention parameters is reported. The 2 programs provide identical predictions of retention data, when predictions are based on two initial exptl. chromatog. measurements. An addnl. option of ChromSword, employing the quant. structure-retention relationships (QSRR), appears to provide satisfactory predictions of the sepn. when mol. structural data along with retention data from a single initial exptl. run are used as inputs. Predictions based on mol. structure alone are not very accurate and are not likely to provide useful sepn. information

Linear and quadratic relationships between retention and organic modifier content in eluent in Reversed Phase High-Performance Liquid Chromatography: A systematic comparative statistical study

Statistical evaluation of linear and quadratic models of chromatographic retention was performed. The relationships describing retention were derived for a set of 23 carefully selected test analytes chromatographed on 18 HPLC columns using methanol-water or acetonitrile- water solutions as mobile phase. It was ascertained whether the square term in the quadratic model improves the description of chromatographic retention in a statistically significant manner. It was also checked whether the retention data extrapolated to a hypothetical neat water eluent (log kw) obtained with the two models and the two organic modifiers are equivalent or should be considered different.The research proved that both models yield similar results and the extrapolated log kw values do not differ statistically significantly in the case of methanol-containing mobile phases. In the case of acetonitrile- water systems the log kw values obtained with linear and quadratic models are normally statistically different. Correlation analysis for log kw vs. log P parameters was performed for data determined on six columns. The best correlations were achieved employing log kw data derived with the linear model for methanol/ water systems

MMP-14 degrades tropoelastin and elastin

Matrix metalloproteinases are a class of enzymes, which degrade extracellular matrix components such as collagens, elastin, laminin or fibronectin. So far, four matrix metalloproteinases have been shown to degrade elastin and its precursor tropoelastin, namely matrix metalloproteinase-2, -7, -9 and -12. This study focuses on investigating the elastinolytic capability of membrane-type 1 matrix metalloproteinase, also known as matrix metalloproteinase-14. We digested recombinant human tropoelastin and human skin elastin with matrix metalloproteinase-14 and analyzed the peptide mixtures using complementary mass spectrometric techniques and bioinformatics tools. The results and additional molecular docking studies show that matrix metalloproteinase-14 cleaves tropoelastin as well as elastin. While tropoelastin was well degraded, fewer cleavages occurred in the highly cross-linked mature elastin. The study also provides insights into the cleavage preferences of the enzyme. Similar to cleavage preferences of matrix metalloproteinases-2, -7, -9 and -12, matrix metalloproteinase-14 prefers small and medium-sized hydrophobic residues including Gly, Ala, Leu and Val at cleavage site P1â. Pro, Gly and Ala were preferably found at P1-P4 and P2â²-P4â² in both tropoelastin and elastin. Cleavage of mature skin elastin by matrix metalloproteinase-14 released a variety of bioactive elastin peptides, which indicates that the enzyme may play a role in the development and progression of cardiovascular diseases that go along with elastin breakdown