MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in KRAS-Mutated Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Chemotherapy, the treatment of choice in non-operable cases, achieves a dismal success rate, raising the need for new therapeutic options. In about 25% of NSCLC, the activating mutations of the KRAS oncogene define a subclass that cannot benefit from tyrosine kinase inhibitors (TKIs). The tumor suppressor miR-16 is downregulated in many human cancers, including NSCLC. The main objectives of this study were to evaluate miR-16 treatment to restore the TKI sensitivity and compare its efficacy to MEK inhibitors in KRAS-mutated NSCLC. Methods: We performed in vitro and in vivo studies to investigate whether miR-16 could be exploited to overcome TKI resistance in KRAS-mutated NSCLC. We had three goals: first, to identify the KRAS downstream effectors targeted by mir-16, second, to study the effects of miR-16 restoration on TKI resistance in KRAS-mutated NSCLC both in vitro and in vivo, and finally, to compare miR-16 and the MEK inhibitor selumetinib in reducing KRAS-mutated NSCLC growth in vitro and in vivo. Results: We demonstrated that miR-16 directly targets the three KRAS downstream effectors MAPK3, MAP2K1, and CRAF in NSCLC, restoring the sensitivity to erlotinib in KRAS-mutated NSCLC both in vitro and in vivo. We also provided evidence that the miR-16–erlotinib regimen is more effective than the selumetinib–erlotinib combination in KRAS-mutated NSCLC. Conclusions: Our findings support the biological preclinical rationale for using miR-16 in combination with erlotinib in the treatment of NSCLC with KRAS-activating mutations.     

Imaging ectopic fat deposition in caenorhabditis elegans muscles using nonlinear microscopy

The elucidation of the molecular mechanisms that lead to the development of metabolic syndrome, a complex of pathological conditions including type‐2 diabetes, hypertension, and cardiovascular diseases, is an important issue with high biological significance and requires accurate methods capable of monitoring lipid storage distribution and dynamics in vivo. In this study, the nonlinear phenomena of second and third harmonic generation (SHG, THG) have been employed simultaneously as label‐free, nondestructive diagnostic techniques, for the monitoring and the complementary three‐dimensional (3D) imaging and analysis of the muscular areas and the lipid content localization. THG microscopy was used as a quantitative tool in order to record the accumulation of lipids in nonadipose tissues in the pharyngeal muscles of 18 Caenorhabditis elegans (C. elegans) specimens, while the SHG imaging provided the detailed anatomical information about the structure of the muscles. The ectopic accumulation of fat on the pharyngeal muscles increases in wild‐type (N2) C. elegans between 1 and 9 days of adulthood. This suggests a correlation of ectopic fat accumulation with the process of aging. Our results can contribute to the unraveling of the link between the deposition of ectopic fat and aging, but mainly to the validation of SHG and THG microscopy modalities as new, noninvasive tools to localize and quantify selectively lipid formation and distribution. Microsc. Res. Tech. 78:523–528, 2015. © 2015 Wiley Periodicals, Inc.     

French Fries oleuropein content during the successive deep frying in oils enriched with an olive leaf extract

Olive oil, sunflower oil and soybean oil were enriched with an olive (Olea Europaea) leaf extract rich in oleuropein at a supplementation level of 100 mg total phenolics per kg oil. Supplemented oils were used for deep frying of potatoes for eight successive frying sessions without replenishment under domestic frying conditions. Supplemented oils contained oleuropein while deep frying resulted in a gradual decrease in oils oleuropein content. After the eighth successive frying, oleuropein was still detected in oils, its retention being 3.2–12.4%. Deep frying of potatoes in supplemented oils succeeded in preparing French fries containing oleuropein even after eight successive fryings. Contrary to the oil type, the number of frying sessions affected potatoes oleuropein content. Oleuropein intake by consuming French fries deep‐fried in enriched oils was approximately ten times higher in potatoes prepared in the first frying session as compared to the respective intake after the eighth frying.