RESUMEN
BACKGROUND: Cancer strongly impacts on patients' lives, undermining their life skills. This research aimed to explore the perception of efficacy of participants in a series of expressive-creative workshops (ArtLab) designed to reactivate life skills in cancer patients. METHODS: Quotations of two semi-structured focus groups with ten participants in ArtLab (Mean Age = 59; SD = 11.19) enrolled at [Fondazione IRCCS Istituto Nazionale dei Tumori] have been analyzed through a priori (top-down) thematic analysis which allowed us to identify life skills provided by WHO 1948: Emotional, Relational and Cognitive. RESULTS: Thematic analysis showed ArtLab program's effectiveness, especially regarding Emotional and Relational life skills. Cognitive skills, instead, seemed to be only partially expressed. Sub-themes articulation for each life skill has been discussed. CONCLUSION: This study provides encouraging results with respect to the effectiveness of expressive-creative group workshops among cancer patients.
Asunto(s)
Neoplasias , Humanos , Persona de Mediana Edad , Neoplasias/terapia , Investigación Cualitativa , Grupos FocalesRESUMEN
Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc metallopeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate in the nervous system. Inhibition of GCPII has the potential to reduce extracellular glutamate and represents an opportune target for treating neurological disorders in which excess glutamate is considered pathogenic. Furthermore, GCPII was found to be identical to a tumor marker, prostate-specific membrane antigen (PSMA), and has drawn significant interest as a diagnostic and/or therapeutic target in oncology. Over the past 15 years, tremendous efforts have been made in the discovery of potent GCPII inhibitors, particularly those with phosphorus-, urea- and thiol-based zinc binding groups. In addition, significant progress has been made in understanding the three-dimensional structural characteristics of GCPII in complex with various ligands. The purpose of this review article is to analyze the structure-activity relationships (SAR) of GCPII inhibitors reported to date, which are classified on the basis of their zinc-binding group. SAR and crystallographic data are evaluated in detail for each of these series to highlight the future challenges and opportunities to identify clinically viable GCPII inhibitors.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Glutamato Carboxipeptidasa II/metabolismo , Relación Estructura-Actividad , Animales , Dipéptidos/metabolismo , Glutamato Carboxipeptidasa II/química , Humanos , Modelos MolecularesRESUMEN
1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC(50) values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Fenantridinas/síntesis química , Fenantridinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Inhibidores Enzimáticos/química , Fenantridinas/química , Relación Estructura-ActividadRESUMEN
A method based on single column ion chromatography with UV detection was developed for purity testing and assay of monosodium olpadronate. The analyte aqueous solution is precipitated with methanol to enhance the impurities/olpadronate molar ratio, thus improving purity determination at trace levels. The resulting solution is injected into a standard chromatographic system with UV detector in indirect mode with a Waters IC Pak HR column using diluted nitric acid as the mobile phase. The method was fully validated according to ICH guidelines for the determination of phosphite, phosphate, chloride and methanesulfonic acid in olpadronate being suitable for purity testing and assay.
Asunto(s)
Cloruros/análisis , Cromatografía por Intercambio Iónico/métodos , Difosfonatos/análisis , Mesilatos/análisis , Fosfatos/análisis , Fosfitos/análisis , Sensibilidad y Especificidad , Espectrofotometría UltravioletaRESUMEN
[formula: see text] Catalytic acylation using complex transition metal salts MCo(CO)4 is demonstrated. Surprisingly, a solvent-dependent mechanistic "switch" results in a Lewis acid-based acylation mechanism in nonpolar media and a nucleophilic mechanism in polar organic media. These observations lead to the first example of a catalyzed Staudinger reaction to form beta-lactams.