85 research outputs found
Euro Surveill
In September 2023, a severe outbreak of type B botulism with fifteen cases was linked to consumption of canned sardines at a restaurant in Bordeaux, France, during the Rugby World Cup. The cases were from seven countries. One death was recorded. Outbreak investigation using credit card data, rapid communication between health authorities of the affected countries and broad media communication allowed identification of cases and exposed persons and prevented further severe outcomes
Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers
Background and aims:Â Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Approach and results:Â Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.Conclusions:Â As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.</p
Elaboration d'un algorithme génétique pour l'étude de la similarité entre ligands pour les récepteurs benzodiazépiniques
Développement d'un algorithme génétique original pour l'alignement de graphes moléculaires issus de la densité électronique
Influence of Conformation on the Representation of Small Flexible Molecules at Low Resolution:Alignment of Endothiapepsin Ligands
Development of a Genetic Algorithm Method Applied to the Study of the Similarity between Ligands for the Benzodiazepine Receptors
Application of multiresolution analyses to electron density maps:A critical point analysis approach for the comparison of molecules
Développement d'algorithmes génétiques originaux appliqués à la comparaison moléculaire et à l'élucidation de pharmacophores
Topological Analysis Approach for the Comparison of Structurally Different Molecules - Applications to Benzodiazepine-Related Compounds
Développement d'algorithmes génétiques originaux appliqués à la comparaison moléculaire et à l'élucidation de pharmacophores
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