Potential role in bone regeneration of a novel PTH family member absent in placental mammals

Trabajo presentado en el American Society for Cell Biology (ASCB) Annual Meeting: Stem Cell Biology in Regeneration: Mechanistic Insights from the Zebrafish, celebrado en California (Estados Unidos), el 7 de noviembre de 2014.Peer reviewe

Phosphorus nutritional requirements for fish skeletal development. New insights from zebrafish

Póster presentado en la 9th European Zebrafish Meeting, celebrada en Oslo, Noruega, del 28 de junio al 2 de julio de 2015Nowadays the main concern in fish farming is improvement of the foods used and the reduction of nutrients excreted in the water. In fish, the only route for inorganic phosphate entry is the diet. However, any excess of this nutrient in the diet above the optimal requirement for fish will be excreted. The excess of unused/excreted inorganic phosphate is the origin of most dissolved inorganic waste resulting from intensive fish farming. As consequence, high level of Pi in the effluents of aquaculture systems leads to eutrophication of the aquatic ecosystems. Phosphorus, in the form of inorganic phosphate is involved in multitude of physiological processes and its deficiency has been shown to be responsible of defective mineralization of bones as well as disturbances of intermediary metabolism especially energy metabolism, leading to impairment of growth. It is therefore critical to know precisely the dietary requirement of inorganic phosphate in order to minimize excess phosphorus in diet without risking phosphorus deficiency in cultured fish. In order to understand animal requirements and establish new feed formulations under changing environments it is essential to characterize the regulation of phosphate homeostasis in fish. We have isolated and characterized a new parathyroid hormone (PTH) family member, named PTH4, that it is involved in bone mineral homeostasis in zebrafish. We have found that this new neuropeptide is synthesized by two clusters of neurons specifically located in lateral hypothalamus as shown by whole mount in situ hybridization. Functional studies using a stable transgenic zebrafish lines and MOs knockdown have revealed PTH4 as a powerful regulator of bone mass accrual acting on phosphate homeostasis. Our results, therefore, define a new neural brain-to-bone pathway involving signals from hypothalamus to receptors on bone cells controlling phosphate homeostasis.This work was funded by the Spanish Science and Innovation Ministry project ALG2011-23581 to JR. Paula Suarez Bregua was supported by Campus Do Mar-Xunta de Galicia PhD fellowshipPeer Reviewe

Characterization of a new fish-derived bioactive neuropeptide involved in bone remodelling. Its physiological function and therapeutic potential

Trabajo presentado en la IV International Meeting on Marine Research (IMMR 2014), celebrada en Peniche (Portugal) el 10 y 11 de julio de 2014.Peer reviewe

Phosphorus nutritional requirements for fish skeletal development. New insights from zebrafish

Trabajo presentado en el 9th European Zebrafish Meeting, celebrado en Oslo (Noruega), del 28 de junio al 2 de julio de 2015Nowadays the main concern in fish farming is improvement of the foods used and the reduction of nutrients excreted in the water. In fish, the only route for inorganic phosphate entry is the diet. However, any excess of this nutrient in the diet above the optimal requirement for fish will be excreted. The excess of unused/excreted inorganic phosphate is the origin of most dissolved inorganic waste resulting from intensive fish farming. As consequence, high level of Pi in the effluents of aquaculture systems leads to eutrophication of the aquatic ecosystems. Phosphorus, in the form of inorganic phosphate is involved in multitude of physiological processes and its deficiency has been shown to be responsible of defective mineralization of bones as well as disturbances of intermediary metabolism especially energy metabolism, leading to impairment of growth. It is therefore critical to know precisely the dietary requirement of inorganic phosphate in order to minimize excess phosphorus in diet without risking phosphorus deficiency in cultured fish. In order to understand animal requirements and establish new feed formulations under changing environments it is essential to characterize the regulation of phosphate homeostasis in fish. We have isolated and characterized a new parathyroid hormone (PTH) family member, named PTH4, that it is involved in bone mineral homeostasis in zebrafish. We have found that this new neuropeptide is synthesized by two clusters of neurons specifically located in lateral hypothalamus as shown by whole mount in situ hybridization. Functional studies using a stable transgenic zebrafish lines and MOs knockdown have revealed PTH4 as a powerful regulator of bone mass accrual acting on phosphate homeostasis. Our results, therefore, define a new neural brain-to-bone pathway involving signals from hypothalamus to receptors on bone cells controlling phosphate homeostasis.This work was funded by the Spanish Science and Innovation Ministry project ALG2011-23581 to JR. Paula Suarez Bregua was supported by Campus Do Mar-Xunta de Galicia PhD fellowshipPeer reviewe

Publicación: Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner