RESUMEN
Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.
Asunto(s)
Acetofenonas/farmacología , Actomiosina/metabolismo , Citoesqueleto , Metástasis de la Neoplasia/fisiopatología , Actinas/metabolismo , Animales , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Femenino , Células HCT116 , Humanos , Ratones , Ratones DesnudosRESUMEN
BACKGROUND: Daily disposable contact lenses are gaining in popularity among practitioners and wearers for the improved ocular health and subjective outcomes they offer. Recently a novel daily disposable contact lens material with water gradient technology was introduced. Delefilcon A lenses consist of a 33% water content silicone hydrogel core and an outer hydrogel layer which is totally free of silicone and contains 80% water. METHODS: The aim of the present study was to confirm the layered structure of delefilcon A contact lenses. Thickness of hydrogel coating on the silicone hydrogel core was assessed using Raman spectroscopy. To investigate the layered structure of the material, depth spectra of the lenses were recorded. RESULTS: The results obtained suggest that at about 6 µm a boundary between the hydrogel layer and silicone hydrogel core exists, which is in good agreement with the manufacturer's data. CONCLUSIONS: Data collected in this experiment confirm a water gradient at the delefilcon A lens surface.