The unique Pt(II)-induced nucleolar stress response and its deviation from DNA damage response pathways.

The mechanisms of action for the platinum compounds cisplatin and oxaliplatin have yet to be fully elucidated, despite the worldwide use of these drugs. Recent studies suggest that the two compounds may be working through different mechanisms, with cisplatin inducing cell death via the DNA damage response (DDR) and oxaliplatin utilizing a nucleolar stress-based cell death pathway. While cisplatin-induced DDR has been subject to much research, the mechanisms for oxaliplatin's influence on the nucleolus are not well understood.

Swirls and scoops: Ice base melt revealed by multibeam imagery of an Antarctic ice shelf.

Knowledge gaps about how the ocean melts Antarctica's ice shelves, borne from a lack of observations, lead to large uncertainties in sea level predictions. Using high-resolution maps of the underside of Dotson Ice Shelf, West Antarctica, we reveal the imprint that ice shelf basal melting leaves on the ice. Convection and intermittent warm water intrusions form widespread terraced features through slow melting in quiescent areas, while shear-driven turbulence rapidly melts smooth, eroded topographies in outflow areas, as well as enigmatic teardrop-shaped indentations that result from boundary-layer flow rotation.

Click-Capable Phenanthriplatin Derivatives as Tools to Study Pt(II)-Induced Nucleolar Stress.

It is well established that oxaliplatin, one of the three Pt(II) anticancer drugs approved worldwide, and phenanthriplatin, an important preclinical monofunctional Pt(II) anticancer drug, possess a different mode of action from that of cisplatin and carboplatin, namely, the induction of nucleolar stress. The exact mechanisms that lead to Pt-induced nucleolar stress are, however, still poorly understood. As such, studies aimed at better understanding the biological targets of both oxaliplatin and phenanthriplatin are urgently needed to expand our understanding of Pt-induced nucleolar stress and guide the future design of Pt chemotherapeutics.

Comparison of click-capable oxaliplatin and cisplatin derivatives to better understand Pt(ii)-induced nucleolar stress.

Pt(ii) chemotherapeutic complexes have been used as predominant anticancer drugs for nearly fifty years. Currently there are three FDA-approved chemotherapeutic Pt(ii) complexes: cisplatin, carboplatin, and oxaliplatin. Until recently, it was believed that all three complexes induced cellular apoptosis through the DNA damage response pathway.