RESUMEN
BACKGROUND: Testicular cancer is the most common cancer in young men in developed countries. In adults, international variation in testicular cancer incidence rates has been well-described, while previous research on pediatric and adolescent testicular cancer has been more geographically limited. METHODS: In this analysis, we used data from the three most recent volumes of Cancer Incidence in Five Continents (CI5) and the National Cancer Institute's SEER 18 registries to compare incidence rates for testicular cancer in children (ages 0-14) and adolescents and young adults (AYA; ages 15-39). RESULTS: We find that geographic incidence patterns in AYA are different from patterns in children under 15. In AYA, incidence is highest in Europe (137.4 per million), followed by Oceania (116.9 per million), North America (94.9 per million), South and Central America (66.5 per million), and lowest in Asia (27.1 per million). In contrast, childhood incidence is highest in Asia (4.2 per million) and South America (5.0 per million) and lowest in Europe (2.1 per million) and North America (2.5 per million). In the United States, patterns in incidence rates in racial and ethnic groups mirror international rates. CONCLUSION: These differences in incidence rate variations in pediatric and AYA testicular cancer are intriguing and may aid in understanding the different etiologies of testicular cancer by age group.
Asunto(s)
Etnicidad/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Neoplasias Testiculares/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Agencias Internacionales , Masculino , Adulto JovenRESUMEN
Phosphatidylserine (PS) has previously been found to bind Cu2+ in a ratio of 1 Cu2+ ion per 2 PS lipids to form a complex with an apparent dissociation constant that can be as low as picomolar. While the affinity of Cu2+ for lipid membranes containing PS lipids has been well characterized, the structural details of the Cu-PS2 complex have not yet been reported. Coordinating to one amine and one carboxylate moiety on two separate PS lipids, the Cu-PS2 complex is unique among ion-lipid complexes in its ability to adopt both cis and trans conformations. Herein, we determine which stereoisomer of the Cu-PS2 complex is favored in lipid bilayers using density functional theory calculations and electron paramagnetic resonance experiments. It was determined that a conformation in which the nitrogen centers are cis to each other is the preferred binding geometry. This is in contrast to the complex formed when two glycine molecules bind to Cu2+ in bulk solution, where the cis and trans isomers exist in equilibrium, indicating that the lipid environment has a significant steric effect on the Cu2+ binding conformation. These findings are relevant for understanding lipid oxidation caused by Cu2+ binding to lipid membrane surfaces and will help us understand how ion binding to lipid membranes can affect their physical properties.
Asunto(s)
Cobre/química , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Fosfatidilserinas/química , Cationes Bivalentes , Espectroscopía de Resonancia por Spin del Electrón , Concentración de Iones de Hidrógeno , Oxidación-Reducción , Teoría Cuántica , Estereoisomerismo , TermodinámicaRESUMEN
In this study we developed a sensitive method using high performance liquid chromatography (HPLC) coupled to electrospray ionization (ESI) with high resolution time of flight (TOF) mass spectrometry (MS) for the determination of naturally occurring antioxidant trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene, RES). This method enabled an investigation of a relationship between tumor growth in rats and concentration of RES and its primary metabolites, trans-resveratrol-3-O-sulfate-3-O-sulfate (R3S) and trans-resveratrol-3-O-ß-d-glucuronide (R3G), in rat serum after RES exposure (5 or 25mg/kg/day). RES levels in rat serum were near the limit of detection, showing concentrations of 4±1 and 12±4ng/mL for low and high-dose exposure, respectively. Compared to RES, higher concentrations were found for its metabolites (R3G:4.8±0.3 and 6.8±0.3µg/mL; R3S:0.27±0.09 and 0.34±0.04µg/mL, respectively). Using TOF, for the first time, we measured the matrix affected limits of detection (LODs) in plasma (3.7, 82.4, and 4.7ng/mL for RES, R3G, and R3S, respectively), which were comparable to those reported in previous work using HPLC tandem mass spectrometry, but with a benefit of a full mass spectral profile. The ability to acquire data in full scan mode also revealed other isomers of R3S. The additional novelty of our study is in synthesis and application of deuterated recovery standards enabling accurate and precise quantification. In order to develop a robust method, the ESI conditions were optimized using a multilevel full factorial design of experiments.