RESUMEN
Objective: To identify the therapeutic efficacy of lithium chloride (LiCl) on phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient tumors. Methods: First, the Catalogue of Somatic Mutations in Cancer for mutation spectrum of human endometrial carcinoma samples was analyzed. Second, the relationship between PTEN abundance and LiCl inhibition of endometrial cancer cell lines using Pten(+/+) and Pten(-/-) mouse embryonic fibroblast (MEF) lines was investigated. Moreover, potential alterations of mammalian target of rapamycin (mTOR) signaling pathway after treatment with LiCl were checked.Last,LiCl's efficacy on PTEN null tumors was studied. Results: PTEN was mutated in 39% of endometrial carcinomas. LiCl preferentially inhibited the proliferation of PTEN-deficient endometrial carcinoma cells and MEFs. Furthermore, LiCl blocked PTEN-deficient tumor development. Mechanistically, LiCl down-regulated mTOR signaling. Conclusions: PTEN is the most frequently mutated gene in endometrial carcinoma.By targeting mTOR signaling pathway,LiCl is a promising regimen for the treatment of tumors with PTEN deficiency.
Asunto(s)
Neoplasias Endometriales , Animales , Cromosomas , Femenino , Humanos , Cloruro de Litio , Ratones , Fosfohidrolasa PTEN , Transducción de Señal , TensinasRESUMEN
Vestibular-only neuronal responses to angular acceleration have been systematically characterized in the rostral fastigial nucleus (FN) by several studies. However, responses of these neurons to linear acceleration have not been examined. In this study, we recorded single-unit activity of vestibular-only neurons in an alert monkey during pure sinusoidal linear acceleration along different directions in the horizontal plane. Spatiotemporal response properties were quantified by computing two-dimensional response ellipses in the horizontal plane. Based on this analysis, neurons were classified as narrowly or broadly tuned. About 29% (5/17) of neurons were broadly tuned. The other 71% (12/17) were narrowly tuned. Unlike vestibular nuclei neurons, all recorded FN neurons exhibited irregular resting discharge rates (CV*0.2). Based on studies of linear motion-sensitive neurons in the vestibular nuclei, the data suggest that irregular neurons in the rostral FN and the vestibular nuclei have similar responses to linear acceleration in behaving monkeys.