Biomarkers of clinical benefit for anti-epidermal growth factor receptor agents in patients with non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) remains by far the major cause of cancer-related death in the Western world in both men and women. The majority of patients will be diagnosed with metastatic disease, and chemotherapy doublets remain the cornerstone of treatment for these patients. However, chemotherapy has a minimal impact on long-term survival and prognosis remains poor for these patients. Further improvement in treatment is likely to require incorporation of novel targeted therapies. Among these agents, inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated significant activity in the first-, second- or third-line treatment of NSCLC. The purpose of current paper is to present the evidence for using several proposed molecular biomarkers as a tool for selection of NSCLC patients for anti-EGFR treatment. According to current data, EGFR mutation status appears to be the strongest predictor for the selection of NSCLC patients to first-line treatment with EGFR tyrosine kinase inhibitors vs chemotherapy. Use of other biomarkers remains investigational

The positive role of hope on the relationship between loneliness and unhappy conditions in Hungarian young adults: How pathways thinking matters!

In this study, we examined loneliness and hope components as predictors of unhappy conditions (viz., anxious symptoms, depressive symptoms, & suicidal ideation) in young adults. The sample was comprised of 489 Hungarian college students. Results of conducting hierarchical regression analyses indicated that loneliness and hope pathways (but not hope agency) were important unique predictors of anxious symptoms, depressive symptoms, and suicidal ideation. Moreover, in part, consistent with the notion that hope might buffer the negative effects of loneliness on unhappy conditions, evidence for a significant Loneliness × Hope Pathways interaction effect in predicting each of the three indices of unhappy conditions was found. In contrast, the Loneliness × Hope Agency interaction effect was not found to be significant. Some implications of the present findings for the study and treatment of unhappy conditions in adults are discussed

A fast radio burst localized to a massive galaxy

Intense, millisecond-duration bursts of radio waves (named fast radio bursts) have been detected from beyond the Milky Way. Their dispersion measures—which are greater than would be expected if they had propagated only through the interstellar medium of the Milky Way—indicate extragalactic origins and imply contributions from the intergalactic medium and perhaps from other galaxies. Although several theories exist regarding the sources of these fast radio bursts, their intensities, durations and temporal structures suggest coherent emission from highly magnetized plasma. Two of these bursts have been observed to repeat, and one repeater (FRB 121102) has been localized to the largest star-forming region of a dwarf galaxy at a cosmological redshift of 0.19 (refs. 7,8,9). However, the host galaxies and distances of the hitherto non-repeating fast radio bursts are yet to be identified. Unlike repeating sources, these events must be observed with an interferometer that has sufficient spatial resolution for arcsecond localization at the time of discovery. Here we report the localization of a fast radio burst (FRB 190523) to a few-arcsecond region containing a single massive galaxy at a redshift of 0.66. This galaxy is different from the host of FRB 121102, as it is a thousand times more massive, with a specific star-formation rate (the star-formation rate divided by the mass) a hundred times smaller

RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation

Background: A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC. Methods: Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N = 36) and (b) within discordant ASC MZ twin pairs (total N = 11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis. Results: In the discordant twin analysis, three genes showed evidence for DE at FDR < 10%: IGHG4, EVI2A and SNORD15B. In the case-control analysis, four DE genes were identified at FDR<10% including IGHG4, PRR13P5, DEPDC1B, and ZNF501. We find enrichment for DE of genes curated in the SFARI human gene database. Pathways showing evidence of enrichment included those related to immune cell signalling and immune response, transcriptional control and cell cycle/proliferation. Integrative methylomic and transcriptomic analysis identified a number of genes showing suggestive evidence for cis dysregulation. Limitations: Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis. Conclusions: Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals