NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Synthesis of Pyrrolidine-2-ylidenes from Isoxazolines and Allenes.

A diastereoselective addition and rearrangement reaction has been developed for the synthesis of pyrrolidine-2-ylidenes from N-isoxazolines and electron-deficient allenes. This method proceeds via the rearrangement of a proposed -alkenylisoxazoline intermediate to generate densely functionalized pyrrolidine-2-ylidenes under simple catalyst-free conditions that tolerate ketone substituents and install relative stereochemistry at positions 3 and 4 of the heterocycle. Reaction optimization and the substrate scope are described in addition to studies evaluating the reactivity of the -dione and enaminone groups of the products.

TRAIL-induced cytokine production via NFKB2 pathway promotes neutrophil chemotaxis and immune suppression in triple negative breast cancers.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that induces apoptosis in cancer cells while sparing the non-malignant cells in preclinical models. However, its efficacy in clinical trials has been limited, suggesting unknown modulatory mechanisms responsible for the lack of TRAIL activity in patients. Here, we hypothesized that TRAIL treatment elicits transcriptional changes in triple negative breast cancer (TNBC) cells that alter the immune milieu.

Students' Experiences with the Science and Engineering Practices in a Workshop-Based Undergraduate Research Experience.

This paper presents a phenomenographic investigation on students' experiences about research and poster presentations in a workshop-based undergraduate research experience with a focus on how the experience connects to the Science and Engineering Practices (SEPs) of the NRC and the principles of CUREs. This provides insight into how these structured research experiences reflect particular SEPs and also elements of scientific practice that are not captured in the SEPs as they have been formulated previously. This work showcases the importance of future applications, failure, and creativity as additional science practices necessary for students to engage in authentic science.