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Using piezoelectric bionanomaterials to promote the generation of reactive oxygen species (ROS) is being increasingly recognized in ultrasound (US)‐triggered tumor treatments. The mechanism underlying this innovative treatment involves US irradiation, which activates the built‐in electric field (BIEF) and induces energy‐band bending in piezoelectric materials (PEMs). In this study, Sr0.5Ba0.5Nb2O6 (SBN) nanorods (NRs) are synthesized using a molten salt method. Subsequently, oxygen‐vacancy (OV)‐rich SBN/Sr2Nb2O7 (SBN/SNO) heterojunction nanocomposites (NCs) are fabricated via H2 annealing of the SBN NRs. The engineering strategy focused on enhancing ROS generation, thereby augmenting the piezoelectric catalytic activity of the NCs. This configuration ensures that the BIEF and heterojunction‐induced field act synergistically to provide a sustained driving force for the separation of electron‐hole (e−‐h+) pairs. Importantly, the OVs on the surfaces of the H2‐annealed SBN NRs create electron‐rich sites, which substantially enhance their piezocatalytic capabilities. In vitro and in vivo analyses of hepatocellular carcinoma (HCC) models demonstrate the significant cytotoxic and tumor‐inhibitory capabilities of this rich OV‐mediated sonopiezoelectric therapy (SPT) and illustrate its potential as a promising therapeutic approach against cancer. [ABSTRACT FROM AUTHOR]

The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib. ROS1 inhibitors induced mitotic abnormalities and multinucleation in E-cadherin-defective cells, phenotypes associated with a defect in cytokinesis and aberrant p120 catenin phosphorylation and localization. In vivo, ROS1 inhibitors produced profound antitumor effects in multiple models of E-cadherin-defective breast cancer. These data therefore provide the preclinical rationale for assessing ROS1 inhibitors, such as the licensed drug crizotinib, in appropriately stratified patients.Significance: E-cadherin defects are common in breast cancer but are currently not targeted with a precision medicine approach. Our preclinical data indicate that licensed ROS1 inhibitors, including crizotinib, should be repurposed to target E-cadherin-defective breast cancers, thus providing the rationale for the assessment of these agents in molecularly stratified phase II clinical trials. Cancer Discov; 8(4); 498-515. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 371.

We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 mutant clones. Random barcode sequences were inserted into the transposon vector to allow the number of cells bearing each insertion to be measured by amplifying and sequencing the barcodes. These barcodes were associated with their integration sites by inverse PCR. We exposed these libraries to commonly used cancer drugs and profiled changes in barcode abundance by Ion Torrent sequencing in order to identify mutations that conferred sensitivity. Drugs tested included conventional chemotherapeutics as well as targeted inhibitors of topoisomerases, poly(ADP-ribose) polymerase (PARP), Hsp90 and WEE1.

Epithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy. [ABSTRACT FROM AUTHOR]

Phytohormones have the potential to enhance the nutrient removal efficiency of aquatic plants in wastewater treatment. Here, we investigated the impact of indoleacetic acid (IAA) on nitrogen removal by Hydrocotyle vulgaris Lam during the remediation process of eutrophic water. This investigation involved evaluating the biological indicators of H. vulgaris Lam, the nitrogen salt removal efficiency in eutrophic water, as well as analyzing the bacterial structure and function in both the rhizosphere and eutrophic water surrounding H. vulgaris Lam. The results indicated that surface-sprayed 50 mg/L IAA significantly stimulated the growth of H. vulgaris Lam, including parameters such as blade number, leaf area, petiole length, stem thickness, stem length, and root length of H. vulgaris Lam. Furthermore, exogenous application of IAA significantly accelerated the nitrogen removal of NH4+−N, NO3−−N and total nitrogen (TN) in eutrophic water by promoting the NH4−N uptake of H. vulgaris Lam and NO3−−N denitrification. These findings suggest a potential application for exogenous IAA to enhance the nitrogen removal of H. vulgaris Lam in eutrophication control. [ABSTRACT FROM AUTHOR]