RESUMEN

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

RESUMEN

While the majority of children with febrile seizures have an excellent prognosis, a small percentage are later discovered to have cognitive impairment. Whether the febrile seizures produce the cognitive deficits or the febrile seizures are a marker or the result of underlying brain pathology is not clear from the clinical literature. We evaluated hippocampal and prefrontal cortex function in adult rats with a prior history of experimental febrile seizures as rat pups. All of the rat pups had MRI brain scans following the seizures. Rats subjected to experimental febrile seizures were found to have moderate deficits in working and reference memory and strategy shifting in the Morris water maze test. A possible basis for these hippocampal deficits involved abnormal firing rate and poor stability of hippocampal CA1 place cells, neurons involved in encoding and retrieval of spatial information. Additional derangements of interneuron firing in the CA1 hippocampal circuit suggested a complex network dysfunction in the rats. MRI T2 values in the hippocampus were significantly elevated in 50% of seizure-experiencing rats. Learning and memory functions of these T2-positive rats were significantly worse than those of T2-negative cohorts and of controls. We conclude that cognitive dysfunction involving the hippocampus and prefrontal cortex networks occur following experimental febrile seizures and that the MRI provides a potential biomarker for hippocampal deficits in a model of prolonged human febrile seizures.

Asunto(s)

Trastornos del Conocimiento/etiología , Convulsiones Febriles/complicaciones , Potenciales de Acción/fisiología , Análisis de Varianza , Animales , Animales Recién Nacidos , Encéfalo/patología , Encéfalo/fisiopatología , Mapeo Encefálico , Trastornos del Conocimiento/patología , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Aprendizaje por Laberinto/fisiología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/fisiología , Percepción Espacial/fisiología

RESUMEN

We use pore fluid measurements of the chloride concentration and the oxygen isotopic composition from Ocean Drilling Program cores to reconstruct salinity and temperature of the deep ocean during the Last Glacial Maximum (LGM). Our data show that the temperatures of the deep Pacific, Southern, and Atlantic oceans during the LGM were relatively homogeneous and within error of the freezing point of seawater at the ocean's surface. Our chloride data show that the glacial stratification was dominated by salinity variations, in contrast with the modern ocean, for which temperature plays a primary role. During the LGM the Southern Ocean contained the saltiest water in the deep ocean. This reversal of the modern salinity contrast between the North and South Atlantic implies that the freshwater budget at the poles must have been quite different. A strict conversion of mean salinity at the LGM to equivalent sea-level change yields a value in excess of 140 meters. However, the storage of fresh water in ice shelves and/or groundwater reserves implies that glacial salinity is a poor predictor of mean sea level.