Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs.

A genome-wide analysis of colorectal cancer in a child with Noonan syndrome.

Noonan syndrome (NS) is a developmental syndrome caused by germline mutations in the Ras signaling pathway. No association has been shown between NS and pediatric colorectal cancer (CRC). We report the case of CRC in a pediatric patient with NS.

Scalaradial Is a Potent Inhibitor of Transient Receptor Potential Melastatin 2 (TRPM2) Ion Channels.

TRPM2 is a Ca-permeable, nonselective cation channel that plays a role in oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2 inhibitors have been reported, which hampers the validation of TRPM2 as a drug target. While screening our in-house marine-derived chemical library, we identified scalaradial and 12-deacetylscalaradial as the active components within an extract of an undescribed species of Cacospongia (class Demospongiae, family Thorectidae) that strongly inhibited TRPM2-mediated Ca influx in TRPM2-overexpressing HEK293 cells.

Activation of store-operated I(CRAC) by hydrogen peroxide.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) play a role in both innate immunity as well as cellular injury. H2O2 induces changes in intracellular calcium ([Ca(2+)]i) in many cell types and this seems to be at least partially mediated by transient receptor potential melastatin 2 (TRPM2) in cells that express this channel. Here we show that low concentrations of H2O2 induce the activation of the Ca(2+)-release activated Ca(2+) current I(CRAC).