Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols

Abstract: Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well‐defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox‐based approaches to cancer therapy

Interlaboratory assessment of marine bioassays to evaluate the environmental quality of coastal sediments in Spain. VI. General analysis of results and conclusions of the exercise

To ensure that toxicity bioassays comply with national criteria, an interlaboratory study was carried out that focussed mainly on the development, optimization and validation of methods for dredged material toxicity assessment. The performance of these techniques was assessed in a validation study and the results were compared with the traditional chemical characterization. This study included two phases and showed promising results in particular for the Microtox® bioassay, the bioassay using crustacean amphipods and the embryo-larval development bioassay using sea urchins. These tests seem feasible and give useful information for dredged material management. Moreover, to evaluate sediment quality, the chemical concentration of the contaminants of concern and toxicity test endpoints were linked using multivariate analysis. The results of this analysis showed that the toxic responses were correlated to different contaminants measured in the sediments

Interlaboratory assessment of marine bioassays to evaluate the environmental quality of coastal sediments in Spain. I. Exercise description and sediment quality

 The results of an interlaboratory assessment made to evaluate the use of different bioassays for sediment quality characterization for a regulatory purpose are presented. The objective of the study was to determine the main differences among sediment bioassays conducted at different laboratories and to evaluate how this can influence dredged material management. The exercise consisted of two parts. During Phase I, six dredged sediment samples from different Spanish ports (Barcelona, Bilbao, Cádiz, Cartagena and Huelva) were distributed to different laboratories where they were applied a screening test for initial toxicity evaluation, a test for elutriates and two solid-phase bioassays. In Phase II, six new sediment samples (from the ports of Algeciras, Bilbao, Cádiz and Huelva) were tested to re-evaluate some bioassays for which different interfering factors were identified during the first phase. The chemical characterization results for Phase I showed high concentrations of some compounds in all the samples except one, which could be considered uncontaminated, while those for Phase II showed high concentrations in most sediments of some metallic compounds, mainly Cu, Hg and As, and to a lesser extent Cd, and of the total polychlorinated biphenyl congeners analyzed. According to Spanish guidelines for dredged material management, only one of the six samples assessed in each phase of the exercise would be suitable for open water disposal