Association of Consensus Molecular Subtypes and Molecular Markers With Clinical Outcomes in Patients With Metastatic Colorectal Cancer: Biomarker Analyses From LUME-Colon 1.

INTRODUCTION: LUME-Colon 1 (NCT02149108) was a global, placebo-controlled phase III study of nintedanib in advanced colorectal cancer (CRC). Pre-specified biomarker analyses investigated the association of CRC consensus molecular subtypes (CMS) and tumor genomic and circulating biomarkers with clinical outcomes. MATERIALS AND METHODS: Archival tumor tissue, cell-free DNA (cfDNA), and plasma samples were collected for genomic, transcriptomic, and proteomic analyses to investigate potential associations between CRC CMS and other biomarkers with nintedanib response and clinical outcomes. RESULTS: Of the 765 treated patients, 735, 245, and 192 patient samples were analyzed in the circulating protein, tumor tissue, and cfDNA datasets, respectively. Patients were classified as CMS1 (1.7%), CMS2 (27.7%), CMS3 (0.9%), CMS4 (51.5%), or unclassified (18.2%). Unclassified/mixed CMS was associated with longer overall survival (OS) with nintedanib vs. CMS2 or CMS4 (interaction P-value = .0086); no association was observed for CMS4. Gene expression-based pathway analysis revealed an association between vascular endothelial growth factor-related signaling and OS for nintedanib (P = .0498). The most frequently detected somatic mutations were APC (72.0% [tumor tissue] vs. 56.8% [cfDNA]), TP53 (47.1% vs. 34.9%), KRAS (40.8% vs. 28.6%), and PIK3CA (16.6% vs. 11.5%); concordance rates were > 80%. Median OS differences were observed for APC and TP53 mutations vs. wild-type in cfDNA, indicating a potential prognostic value. Circulating ANG-2, CA-9, CEACAM1, collagen-IV, IGFBP-1, ICAM-1, IL-8, and uPAR were potentially prognostic for both OS and progression-free survival. CONCLUSION: We demonstrated the feasibility of large-scale biomarker analyses and CMS classification within a global clinical trial, and identified signals suggesting a potential for greater nintedanib treatment response in the unclassified/mixed CMS subgroup, despite these tumors showing heterogeneous patterns of CMS mixtures. Our results revealed a high degree of concordance in somatic mutations between tumor tissue and cfDNA. Associations with prognosis for cfDNA somatic mutations, as well as several protein-based biomarkers, may warrant further investigation in future trials.status: Published onlin

Antifungal and repellent activities of the essential oils from three aromatic herbs from western Himalaya

In this investigation we examined the essential oils of three aromatic plants, Zanthoxylum armatum, Juniperus communis, and Dysphania ambrosioides, which are used by the local population of the western Himalayan region for medicinal purposes. These plants were studied for their antifungal, larvicidal and biting deterrent activities. Additionally, chemical compositions of the oils were determined by GC-MS and their odor evaluated. The main compounds were 2-undecanone (47.7%) and 1,8-cineol (20.5%) from Z. armatum and α-pinene (43.2%) and limonene (34.7%) from J. communis. p-Cymene (36.3%) and ascardiole (31.2%) were found as the main components of D. ambrosioides essential oil. Antifungal activity was evaluated against three Colletotrichum species. Dyspania ambrosioides oil showed the best activity against these strawberry anthracnose causing fungi. It also demonstrated biting deterrent activity against Aedes aegypti similar to DEET as positive control, whereas Z. armatum and J. communis were less effective against Colletotrichum and mosquitoes.© 2018 Iris Stappen et a

Biological Activity of Bunium persicum Essential Oil from Western Himalaya

The essential oil of Bunium persicum collected from cultivated sources in the cold desert area of Lahaul-Spiti is described for its antimicrobial, larvicidal, and biting deterrent activities. Additionally, odor characterization is given. The chemical composition of the essential oil was analyzed by simultaneous GC-MS and GC-FID. γ-Terpinene and p-cymene were found to be the major compounds. Antibacterial testing by an agar dilution assay revealed low activity of the oil against all tested bacteria. Antifungal activity was evaluated against Candida albicans as well as three species of the strawberry anthracnose causing plant pathogen Colletotrichum. Bunium persicum essential oil demonstrated antifungal activity against all four pathogens. Biting deterrent activity against Aedes aegypti was greater than the solvent control, but significantly lower than DEET. The essential oil of B. persicum exhibited larvicidal activity with an LC50 value of 58.6 ppm against Ae. aegypti larvae.© Georg Thieme Verlag K