Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Fate of silica nanoparticles in simulated primary wastewater treatment

Through novel application of small-angle neutron scattering, we examined the fate of silica nanoparticles (SiO2NPs)during simulated primary wastewater treatment, by measuring, in real time, the colloidal behavior of SiO2NPs in wastewater (sewage). We examined the effects of surface functionality on SiO2NP fate in wastewater, by comparing both unfunctionalized (uncoated or “bare”) SiO2NPsand SiO2NPsfunctionalized with a thin coating of a nonionic surfactant (Tween 20), which is widely used in personal care and household product formulations containing engineered oxide nanoparticles. Our results show new evidence that the surface functionality of SiO2NPs plays a crucial role in their flocculation and sedimentation behavior in wastewater, and thus the likely efficacy of their removal from the effluent stream during primary wastewater treatment. Uncoated SiO2NPs did not flocculate in wastewater over typical residence times for primary treatment. Conversely, surface-functionalized (Tween-coated) SiO2NPs underwent rapid flocculation in wastewater. Our results show that the surface-functionalized SiO2NPs are likely to be removed by sedimentation to sewage sludge (typically recycled to land), whereas uncoated SiO2NPs will continue through the effluent stream. While nanoparticle design is driven by use purpose, this study shows new potential for exploiting surface functionalization of nanoparticles to modify their environmental pathways