Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors.

Argininosuccinate synthase (ASS1) downregulation in different tumors has been shown to support cell proliferation and yet, in several common cancer subsets ASS1 expression associates with poor patient prognosis. Here we demonstrate that ASS1 expression under glucose deprivation is induced by c-MYC, providing survival benefit by increasing nitric oxide synthesis and activating the gluconeogenic enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase by S-nitrosylation. The resulting increased flux through gluconeogenesis enhances serine, glycine and subsequently purine synthesis.

A removable partial denture using an esthetically designed round-rest distal clasp on maxillary anterior abutment teeth: a clinical report.

A round-rest, distal depression clasp is suggested as an esthetic alternative to a conventional clasp for maxillary anterior teeth serving as abutments for a removable partial denture. A lingual round rest provides support for the prosthesis, and a mesiolingual reciprocating plate is present. A split minor connector engages a distal depression for retention.