Selective Targeting of Protein Kinase C (PKC)-θ Nuclear Translocation Reduces Mesenchymal Gene Signatures and Reinvigorates Dysfunctional CD8 T Cells in Immunotherapy-Resistant and Metastatic Cancers.

Protein kinase C (PKC)-θ is a serine/threonine kinase with both cytoplasmic and nuclear functions. Nuclear chromatin-associated PKC-θ (nPKC-θ) is increasingly recognized to be pathogenic in cancer, whereas its cytoplasmic signaling is restricted to normal T-cell function. Here we show that nPKC-θ is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma and is associated with poor survival in immunotherapy-resistant disease.

Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans.

The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals. This reveals two B cell lineages: a classical lineage of activated and resting memory B cells and an alternative lineage, which includes previously described atypical B cells.

Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.

Lysine specific demethylase 1 (LSD1) is a key epigenetic eraser enzyme implicated in cancer metastases and recurrence. Nuclear LSD1 phosphorylated at serine 111 (nLSD1p) has been shown to be critical for the development of breast cancer stem cells. Here we show that circulating tumor cells isolated from immunotherapy-resistant metastatic melanoma patients express higher levels of nLSD1p compared to responders, which is associated with co-expression of stem-like, mesenchymal genes.

Relation of postoperative pain medication to return for unplanned care after ureteroscopy.

To determine whether the US Drug Enforcement Agency (DEA) class of narcotics prescribed to patients after ureteroscopy impacts their rate of return for unplanned care, a retrospective analysis of patients from February 2014 through March 2016 was performed. Data were collected for the first 90 days after surgery. Patients were divided into groups based on the narcotics schedule prescribed after surgery.

Comparison of utilization of pressurized automated versus manual hand irrigation during ureteroscopy in the absence of ureteral access sheath.

This study compared patient outcomes following irrigation applied using an automated pressure system (AP) to hand irrigation utilizing a syringe (HI) during ureteroscopy. Retrospective chart review was performed to evaluate ureteroscopy procedures without a ureteral access sheath. Procedures in which irrigation was applied by AP were compared to those with HI.