T-cell immune checkpoint inhibition plus hypomethylation for locally advanced HER2-negative breast cancer: a phase 2 neoadjuvant window trial of decitabine and pembrolizumab followed by standard neoadjuvant chemotherapy.

Background: Higher levels of tumor-infiltrating lymphocytes (TILs) in breast cancers are associated with increased likelihood of pathologic complete response (pCR) to chemotherapy. DNA methyltransferase inhibitors (DNMTi) can augment immune responses to cancers, decreasing myeloid-derived suppressor cells (MDSCs) and increasing T lymphocyte responsiveness. We have shown that the DNMTi decitabine augments the effectiveness of immunotherapy using murine triple-negative breast cancer (TNBC) models.

Use of web-based decision support to improve informed choice for chemoprevention: a qualitative analysis of pre-implementation interviews (SWOG S1904).

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Longitudinal associations among physical activity and sitting with endocrine symptoms and quality of life in breast cancer survivors: A latent growth curve analysis.

Purpose: Adjuvant endocrine therapy (AET) often causes debilitating endocrine symptoms that compromise quality of life (QOL) in women diagnosed with hormone receptor positive breast cancer (BC). We examined whether greater levels of physical activity (PA) or prolonged sitting were associated with reduced side effects or worse side effects of AET, respectively.

Methods: We used parallel process latent growth curve models to examine longitudinal patterns in PA and sitting behaviors, and their association with endocrine symptoms and QOL over 3 years of follow-up in 554 female BC survivors undergoing AET.

Physical activity, health-related quality of life, and adjuvant endocrine therapy-related symptoms in women with hormone receptor-positive breast cancer.

Background: Physical activity (PA) is recommended for women with breast cancer (BC); however, data are sparse on the association of PA with quality of life (QOL) and patient-reported symptoms for women on adjuvant endocrine therapy (AET).

Methods: Women with hormone receptor-positive BC who were taking AET completed standardized surveys about their health-related QOL, AET-related symptoms, and levels of PA using validated measures. A Wald chi-square test and an analysis of variance were used to assess associations with PA and independent variables.

Co-administration of the mTORC1/TORC2 inhibitor INK128 and the Bcl-2/Bcl-xL antagonist ABT-737 kills human myeloid leukemia cells through Mcl-1 down-regulation and AKT inactivation.

Effects of concurrent inhibition of mTORC1/2 and Bcl-2/Bcl-xL in human acute myeloid leukemia cells were examined. Tetracycline-inducible Bcl-2/Bcl-xL dual knockdown markedly sensitized acute myeloid leukemia cells to the dual TORC1/2 inhibitor INK128 in vitro as well as in vivo. Moreover, INK128 co-administered with the Bcl-2/xL antagonist ABT-737 sharply induced cell death in multiple acute myeloid leukemia cell lines, including TKI-resistant FLT3-ITD mutants and primary acute myeloid leukemia blasts carrying various genetic aberrations e.

Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasm.

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is characterized by prolonged severe constriction of the basilar artery, which often leads to ischemic brain damage. Locally elevated concentrations of spasmogenic substances induce persistent depolarization of myocytes in the basilar artery, leading to continuous influx of calcium (Ca) through voltage-sensitive Ca channels and myocyte contraction. Potassium (K) channel openers may have therapeutic utility to oppose membrane depolarization, dilate the arteries, and reduce ischemia.