NOTCH (NICD) signaling is initiated by inducible nitric oxide synthase (iNOS) via ADAM17/transarterial chemoembolization (TACE) activation, resulting in an active NOTCH intracellular domain.46 Interestingly, when three members of the retinoblastoma (RB) family—RB, p107, and p130—were not expressed in the liver, the NOTCH pathway was activated, leading to reduced HCC formation. Here, NOS2 is linked to hepatocellular carcinoma.