RESUMEN
The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer.
Asunto(s)
Neoplasias de la Mama , Podosomas , Humanos , Femenino , Transducción de Señal , Podosomas/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Movimiento Celular , Línea Celular TumoralRESUMEN
The queen scallop Aequipecten opercularis accumulates high concentrations of lead (Pb) in its tissues, what has led to the interruption of this fishery in some extraction areas in Galicia (NW Spain). This study follows the dynamics of bioaccumulation of Pb and other metals in this species, the tissue distribution and the subcellular partitioning in selected organs, in order to understand the mechanisms that provoke the high Pb levels reached in its tissues and to increase our knowledge about metal bioaccumulation dynamics in this species. Scallops originating from a clean area were exposed in cages in two places in the Ría de Vigo (one shipyard and a less impacted location) and 10 individuals were collected every month over a three months period. Metal bioaccumulation and metal distribution in several organs, including gills, digestive gland, kidneys, muscle, gonad and remaining tissues, was studied. The results showed that scallops accumulated similar levels of Cd, Pb and Zn at both sites, while Cu and Ni showed an opposite pattern at the shipyard, with Cu concentrations increasing around 10 times and Ni decreasing during the 3 months of exposure. The preferential organs for metal accumulation were the kidneys for Pb and Zn, the digestive gland for Cd, both organs for Cu and Ni, and the muscle for As. Subcellular partitioning of kidney samples additionally showed an extraordinary ability to accumulate Pb and Zn at very high concentrations in kidney granules, a fraction that accounted for 30 to 60 % of Pb in soft-tissues. It is concluded that Pb bioaccumulation in kidney granules is the mechanism responsible for the high levels of Pb observed in this species.
Asunto(s)
Metales Pesados , Pectinidae , Contaminantes Químicos del Agua , Humanos , Animales , Cadmio , Plomo , Bioacumulación , Alimentos Marinos , Metales Pesados/análisis , Monitoreo del AmbienteRESUMEN
BACKGROUND: Clitoral artery Doppler has been used as an objective technique to measure changes in genital women response. However, the technique has not been fully validated, and arterial volume flow has never been used as an outcome measure. AIMS: To validate the technique clitoral artery Doppler measured in a sagittal section and explore arterial volume flow as a new parameter in clitoral Doppler. METHODS: We examined 90 healthy volunteers by clitoral artery Doppler using the sagittal section approach described by Battaglia et al in 2008. We calculated intraobserver, interobserver, and intraobserver intersession variability and reliability for all Doppler parameters and described and validated arterial volume flow as a new parameter in clitoral artery Doppler. OUTCOMES: We calculated peak systolic velocity (PSV), time-averaged maximum velocity, time-averaged mean velocity, end-diastolic velocity, pulsatility index, resistance index, and volume flow (v-flow) in all groups. We conducted reliability analyses using the intraclass correlation coefficient for agreement. We explored differences between and within observers and calculated agreement limits using the Bland-Altman test. RESULTS: The intraclass correlation coefficient analysis showed correlation values higher than 0.75 (good reliability) for most of the variables and higher than 0.60 (moderate reliability) for the remaining ones. There were statistically significant differences between PSV and time-averaged maximum velocity in the intraobserver intersession measurements. For the remaining groups and variables, no statistically significant differences were observed. Bland-Altman analyses showed that the limits of agreement were acceptable and the regressions were not significant. The v-flow parameter also showed good reliability and low variability between groups. CLINICAL IMPLICATIONS: We found that PSV was not a good outcome measure because of its high intraobserver and intersession variability. Moreover, it is possible to measure v-flow in the clitoral artery using the sagittal technique described by Battaglia et al, and it seems that this measure is reliable and reproducible. This could be the best parameter to assess clinical changes. STRENGTHS & LIMITATIONS: This study provided full validation of the sagittal section approach and of a new parameter, v-flow, which could beuseful for assessing clitoral blood flow. The main limitation of the study is its retrospective nature for validating v-flow. CONCLUSION: We found that clitoral artery Doppler measured using a sagittal approach is a valid and reliable technique for studying clitoral blood flow in women. The v-flow variable is a promising and reliable parameter for measuring changes in clitoral blood flow. Pérez MF, Agís IF, La Calle Marcos P, et al. Validation of a Sagittal Section Technique for Measuring Clitoral Blood Flow: Volume Flow - A New Parameter in Clitoral Artery Doppler. J Sex Med 2020;17:1109-1117.