Purpose This study characterized the therapeutic efficacy of a systemically administered formulation of 3-bromopyruvate (3-BrPA), microencapsulated in a complex with β-cyclodextrin (β-CD), using an orthotopic xenograft mouse model of pancreatic ductal adenocarcinoma (PDAC). Experimental Design The presence of the β-CD–3-BrPA complex was confirmed using nuclear magnetic resonance spectroscopy. Monolayer as well as three-dimensional organotypic cell culture was used to determine the half-maximal inhibitory concentrations (IC50) of β-CD–3-BrPA, free 3-BrPA, β-CD (control), and gemcitabine in MiaPaCa-2 and Suit-2 cell lines, both in normoxia and hypoxia. Phase-contrast microscopy, bioluminescence imaging (BLI), as well as zymography and Matrigel assays were used to characterize the effects of the drug in vitro. An orthotopic lucMiaPaCa-2 xenograft tumor model was used to investigate the in vivo efficacy. Results β-CD–3-BrPA and free 3-BrPA demonstrated an almost identical IC50 profile in both PDAC cell lines with higher sensitivity in hypoxia. Using the Matrigel invasion assay as well as zymography, 3-BrPA showed anti-invasive effects in sublethal drug concentrations. In vivo, animals treated with β-CD–3-BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to animals treated with gemcitabine or the β-CD (60-fold and 140-fold signal increase, respectively). In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for β-CD–3-BrPA. Conclusion The microencapsulation of 3-BrPA represents a promising step towards achieving the goal of systemically deliverable antiglycolytic tumor therapy. The strong anticancer effects of β-CD–3-BrPA combined with its favorable toxicity profile suggest that clinical trials, particularly in patients with PDAC, should be considered.
Synchronous tumors of the pancreas and gallbladder are rare and often attributed to an abnormal pancreato-biliary junction, which results in a persistent reflux of pancreatic secretions leading to chronic biliary inflammation. We present the case of a 73-year-old woman with synchronous lesions of the pancreas and gallbladder initially considered as two primary localized cancers and treated with curative intent. At relapse, targeted next generation sequencing (NGS), performed in search of potential therapeutic targets, uncovered the fact that the two lesions appeared to be clonally related. This case illustrates the problem of synchronous lesions of the pancreas and gallbladder. New pathologic assessments with comparative molecular analysis of mutational profiles may be helpful in this context.
Se han desarrollado distintas técnicas para estimular la consolidación ósea en las seudoartrosis de huesos largos, como el uso de injerto óseo molido o estructural, injertos vascularizados o la técnica de membrana inducida. En 2018, Barrera-Ochoa describió la anatomía de un injerto perióstico vascularizado de cúbito con eje vascular interóseo posterior, y mostró su experiencia clínica inicial en niños utilizándolo en una seudoartrosis atrófica de radio y un defecto óseo después de la exéresis de un tumor de Ewing. Presentamos nuestra experiencia con el injerto perióstico vascularizado de cúbito para el tratamiento de una seudoartrosis recalcitrante en la diáfisis de radio de un paciente adulto.
Objetivo: Comunicar los resultados y las complicaciones a corto plazo de la artropatía del manguito rotador tratada con artroplastia invertida lateralizada en pacientes >60 años. Materiales y Métodos: Se identificaron retrospectivamente las artropatías del manguito rotador tratadas con prótesis invertida lateralizada entre 2015 y 2019. Criterios de inclusión: edad >60 años, adecuada función deltoidea y seguimiento mínimo de 24 meses. Antes de la cirugía y después, se registraron el rango de movilidad activa, y los puntajes de Constant-Murley y de la escala analógica visual para dolor. En las radiografías, se determinaron los grados de artrosis glenohumeral, de muescas escapulares y de aflojamiento de la prótesis. Se documentaron las complicaciones, la satisfacción con el procedimiento y la supervivencia del implante. Resultados: La serie incluyó 40 hombros operados en 38 pacientes (edad promedio 72 años, rango 61-91), con un seguimiento promedio de 25 meses. La elevación anterior aumentó de 82,63° a 136,71° (p <0,001); la rotación externa, de 16,59° a 32,11° (p <0,001) y la rotación interna, de L5 a L3 (p <0,001). El puntaje de Constant-Murley ascendió de 28,25 a 69,97 (p <0,001) y el de dolor disminuyó de 8,34 precirugía a 1,26 poscirugía (p <0,001). La tasa de complicaciones fue del 12,5% y la supervivencia del implante, del 97,4%. Conclusiones: La artroplastia invertida lateralizada es una excelente alternativa quirúrgica para la artropatía del manguito rotador en pacientes >60 años, los resultados son satisfactorios, la tasa de complicaciones es aceptable y la supervivencia del implante es del 97,4%.
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