Identification of BRCA1 As a Potential Biomarker for Insulin-Like Growth Factor-1 Receptor Targeted Therapy in Breast Cancer

The insulin-like growth factor-1 receptor (IGF1R) emerged in recent years as a promising therapeutic target in oncology. Identification of potential biomarkers capable of predicting response to IGF1R-targeted therapy is of cardinal importance. Tumor suppressor BRCA1 has important roles in multiple pathways, including gene transcription, DNA damage repair, and control of apoptosis. Early studies have identified the IGF1R gene as a downstream target for inhibitory regulation by wild-type, but not mutant, BRCA1. The aim of the present study was to evaluate the hypothesis that the mutational status of BRCA1 may influence the ability of IGF1R-directed therapies to efficiently inhibit the IGF1R axis. Using breast cancer-derived cell lines expressing a wild-type or a mutant BRCA1, we demonstrate that the capacity of MK-0646, a monoclonal antibody antagonist to the human IGF1R, to inhibit insulin-like growth factor-1-stimulated IGF1R and downstream mediators’ phosphorylation was impaired in mutant BRCA1-expressing cell lines. In addition, the antibody was able to reduce proliferation of wild-type BRCA1-expressing cells but had a reduced inhibitory effect in mutant BRCA1-expressing cells. In summary, our data indicate that the mutational status of BRCA1 must be taken into account when selecting patients for IGF1R targeting protocols

Nutritional Recommendations for Cardiovascular Disease Prevention

nutrient

Dietary Patterns among Adolescents Are Associated with Growth, Socioeconomic Features, and Health-Related Behaviors

Dietary patterns (DPs), usually established in adolescents, are important modifiable risk factors in the etiology of malnutrition and chronic diseases. This study aimed to identify DPs of adolescents and examine their associations with growth, sociodemographic, and lifestyle characteristics. A nationally representative, school-based, cross-sectional study was conducted in Israeli adolescents aged 11–18 years during 2015–2016. A self-administered survey queried sociodemographics, health behaviors, and diet. Weight and height were measured, and WHO height z-scores and BMI cutoffs were calculated. Food frequency questionnaire data were analyzed using principal components analysis (PCA) to identify DPs. Associations between growth, lifestyle, and sociodemographic characteristics and DPs were modeled using multivariable logistic regressions. A total of 3902 adolescents (46% males, mean age 15.2 ± 1.6 years) completed the survey. PCA identified five DPs, accounting for 38.3% of the total variance. The first two prominent DPs were the ‘plant-based food’ DP, which was associated with the female sex, higher socioeconomic status, overweight/obesity, and healthy lifestyle and the ‘junk food’ DP, which was associated with lower SES, unhealthy lifestyle, and lower height z-scores. Our results elucidate major DPs that strongly correlate with lifestyle risk behaviors and suboptimal growth among adolescents. Implementing screening for DPs should be further examined to identify higher risk health factors among youth

Role of Backbone Charge Rearrangement in the Bond-Dipole and Work Function of Molecular Monolayers

Self-assembled organic monolayers serve for modifying the work function of inorganic substrates. We examine the role of the molecular backbone in determining monolayer-adsorbed work function, by considering the adsorption of dithiols with either a partially conjugated or a saturated backbone on the GaAs(001) surface. Using a combination of chemically resolved electrical measurements based on X-ray photoelectron spectroscopy and contact potential difference, together with first principles electronic structure calculations, we are able to distinguish quantitatively between the contributions of the band bending and surface dipole components. We find that the substrates coated by partially conjugated layers possess a larger band-bending, relative to that of the substrates coated by saturated layers. This is associated with an increased density of surface states, likely related to the presence of oxygen. At the same time, the samples coated by partially conjugated layers also possess a larger bond-dipole, with the difference found to result primarily from an extended charge rearrangement on the molecular backbone. The two effects are, in this case, of opposite sign, but a significant net change in work function is still found. Thus, design of the molecular backbone emerges as an additional and important degree of freedom in the design of potential profiles and charge injection barriers in monolayer-based structures and devices