RESUMO
p53 is an important tumor-suppressor protein that is mutated in more than 50% of cancers. Strategies for restoring normal p53 function are complicated by the oncogenic properties of mutant p53 and have not met with clinical success. To counteract mutant p53 activity, a variety of drugs with the potential to reconvert mutant p53 to an active wildtype form have been developed. However, these drugs are associated with various negative effects such as cellular toxicity, nonspecific binding to other proteins, and inability to induce a wildtype p53 response in cancer tissue. Here, we report on the effects of a curcumin analog, HO-3867, on p53 activity in cancer cells from different origins. We found that HO-3867 covalently binds to mutant p53, initiates a wildtype p53-like anticancer genetic response, is exclusively cytotoxic toward cancer cells, and exhibits high anticancer efficacy in tumor models. In conclusion, HO-3867 is a p53 mutant-reactivating drug with high clinical anticancer potential.
Assuntos
Apoptose/efeitos dos fármacos , Curcumina/análogos & derivados , Proteínas Mutantes/genética , Mutação , Neoplasias/patologia , Piperidonas/farmacologia , Proteína Supressora de Tumor p53/genética , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Curcumina/farmacologia , Feminino , Humanos , Camundongos , Camundongos Nus , Proteínas Mutantes/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Over 212 healthcare professionals from the country have used the online trainings on radiation protection conducted during the COVID-19 pandemic. Each training, lasting up to 10 working days, is accompanied by mandatory Google Form-based questionnaires, which includes topic key questions about each lecture as well as pre- and post-training tests and provided to participants. In addition, the ability to conduct a dialogue with patients about radiation risks, group discussions, as well as a special module for radiation protection officers were assessed online. The trainings also allow participants to focus on the most important issues from their point of view in their daily work, indicating them in pre-tests, allowing the trainers to conduct lectures more adequately for each group of participants. Analysis of the tests have shown that online training is not inferior in efficiency to face-to-face training and national regulatory body received an improved opportunity to indirectly assess this efficiency.