124 research outputs found
Relevance of Fgfr1 and Its Isoforms In Prostate Cancer Bone Metastases
No full textThe fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were obtained when using C4-2B PCa cell line). Also, PC3 PCa cells overexpressing FGFR1 a injected intracardially significantly reduced mouse survival (P = 0.0001) and PCa cells overexpressing FGFR1 a and b increased the incidence of bone metastases (P = 0.00005 and P = 0.025 compared to controls). Accordingly, immunohistochemical analysis of castration-resistant human PCa bone metastases revealed a significant enrichment of FGFR1 expression compared with treatment-naïve, non-metastatic primary tumors (P = 0.0007). Importantly, we demonstrate by RPPA analysis that FGFR1 induces expression of the anchoring filament protein ladinin 1 (LAD1) in PC3 cells. Furthermore, LAD1 gene amplification and LAD1 expression were significantly enriched in castration-resistant human PCa bone metastases (P \u3c 0.0001 and P = 0.0048 respectively) suggesting that LAD1 is implicated in FGFR1-mediated metastases.
In summary, our studies indicate that FGFR1 drives the PCa metastatic phenotype, thus further supporting the development of FGFR blockade as a therapy for metastatic PCa. Our results also suggest that new FGFR1 signatures define pathway activation and this knowledge will help identify markers of pathway inhibition in human PCa. Finally, our findings implicate, for the first time, LAD1 in the metastatic phenotype of a subpopulation of men with PCa
Heme Oxygenase-1 Is a Pivotal Modulator of Bone Turnover and Remodeling: Molecular Implications for Prostate Cancer Bone Metastasis
No full textAims: Bone is the most frequent site of prostate cancer (PCa) metastasis. Tumor cells interact with the bone microenvironment interrupting tissue balance. Heme oxygenase-1 (HO-1; encoded by Hmox1) appears as a potential target in PCa maintaining the cellular homeostasis. Our hypothesis is that HO-1 is implicated in bone physiology and modulates the communication with PCa cells. Here we aimed at (i) assessing the physiological impact of Hmox1 gene knockout (KO) on bone metabolism in vivo and (ii) determining the alterations of the transcriptional landscape associated with tumorigenesis and bone remodeling in cells growing in coculture (PCa cells with primary mouse osteoblasts [PMOs] from BALB/c Hmox1+/+, Hmox1+/-, and Hmox1-/- mice). Results: Histomorphometric analysis of Hmox1-/- mice bones exhibited significantly decreased bone density with reduced remodeling parameters. A positive correlation between Hmox1 expression and Runx2, Col1a1, Csf1, and Opg genes was observed in PMOs. Flow cytometry studies revealed two populations of PMOs with different reactive oxygen species (ROS) levels. The high ROS population was increased in PMOs Hmox1+/- compared with Hmox1+/+, but was significantly reduced in PMOs Hmox1-/-, suggesting restrained ROS tolerance in KO cells. Gene expression was altered in PMOs upon coculture with PCa cells, showing a pro-osteoclastic profile. Moreover, HO-1 induction in PCa cells growing in coculture with PMOs resulted in a significant modulation of key bone markers such as PTHrP and OPG. Innovation and Conclusion: We here demonstrate the direct implications of HO-1 expression in bone remodeling and how it participates in the alterations in the communication between bone and prostate tumor cells.Fil: Anselmino, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Starbuck, Michael. University of Texas; Estados UnidosFil: Labanca, Estefania. University of Texas; Estados UnidosFil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Navone, Nora. University of Texas; Estados UnidosFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Zenclussen, Ana Claudia. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin
La regulación del empleo de los inmigrantes en el Decreto Legislativo n. 286/1998: entre los problemas no resueltos y los intentos de reforma
No full textThe essay analyzes the phenomenon of migration in his role as a structural component of the
Italian labor market. Despite the negative effects of the crisis, the contribution of foreign labor has
to be considered as a valuable resource to restart the competitiveness of enterprises and to
develop the productivity of the economic system. Through an analysis of the regulatory framework
currently in force - also in the light of the most recent legislative changes – the Author highlights
some of the main critical issues of discipline on immigrant labor and reports the possible paths of
reform to be included in the political agenda of the new government.El ensayo analiza el fenòmeno migratorio como elemento estructural del mercado del trabajo
italiano. A pesar los efectos negativos de la crisis, el trabajo extranjero representa todavìa una
preciosa herramienta para la competitividad de las empresas y de la estructura productiva
italiana.
A través de un analisis de las normas hoy en dìa en vigor, como modificadas de recién, se
analizan los principales nodos crìticos de la disciplina de trabajo de los inmigrantes y esboza las
probables reformas de la agenda polìtica del nuevo gobierno
Kind mobile notifications for healthcare professionals
No full textThe inclusion of the Internet of Things in healthcare is producing numerous automatic notifications for health professionals. These notifications must be delivered in the right moment and in the right way to be appropriately attended, and at the same time, ensuring no important task is interrupted. In this work, we have applied a human-centred design method to deal with this issue. By collaborating with health professionals in Belgium, we have designed and validated DELICATE, a conceptual framework that categorizes the different attention needs for each notification, and links them with the delivery mechanisms that are more appropriate for each particular context. As an aid for designers, we also define methodological guidelines to clearly determine how DELICATE can be used to develop a notification system. Finally, as a proof-of-concept validation of the framework, we have implemented it in an Android application and tested it using real scenarios. This validation has shown that DELICATE can be used to design a notification system that delivers kind healthcare notifications.sponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Pedro Valderas's work has been developed with the financial support of the Spanish State Research Agency under the project TIN2017-84094-R and co-financed with ERDF. Estefania Serral and Jan Derboven's work has been supported by IMEC funding. (Spanish State Research Agency|TIN2017-84094-R, ERDF, IMEC)status: Publishe
Myxovirus Resistance Protein 1 (MX1), a Novel HO-1 Interactor, Tilts the Balance of Endoplasmic Reticulum Stress towards Pro-Death Events in Prostate Cancer
No full textThe inflammatory tumor microenvironment is a fertile niche accelerating prostate cancer (PCa). We have reported that heme-oxygenase (HO-1) had a strong anti-tumoral effect in PCa. We previously undertook an in-depth proteomics study to build the HO-1 interactome in PCa. In this work, we used a bioinformatics approach to address the biological significance of HO-1 interactors. Open-access PCa datasets were mined to address the clinical significance of the HO-1 interactome in human samples. HO-1 interactors were clustered into groups according to their expression profile in PCa patients. We focused on the myxovirus resistance gene (MX1) as: (1) it was significantly upregulated under HO-1 induction; (2) it was the most consistently downregulated gene in PCa vs. normal prostate; (3) its loss was associated with decreased relapse-free survival in PCa; and (4) there was a significant positive correlation between MX1 and HMOX1 in PCa patients. Further, MX1 was upregulated in response to endoplasmic reticulum stress (ERS), and this stress triggered apoptosis and autophagy in PCa cells. Strikingly, MX1 silencing reversed ERS. Altogether, we showcase MX1 as a novel HO-1 interactor and downstream target, associated with ERS in PCa and having a high impact in the clinical setting.Fil: Ortiz, Emiliano Germán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sanchis, Pablo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Bizzotto, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lage Vickers, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Labanca, Estefania. University of Texas; Estados UnidosFil: Navone, Nora. University of Texas; Estados UnidosFil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin
EgoRoutine
No full textThe EgoRoutine is the first dataset for behaviour characterisation in egocentric photo-streams. 100k images collected by 7 different users. @article{talavera2020topic, title={Topic Modelling for Routine Discovery from Egocentric Photo-streams}, author={Talavera, Estefania and Wuerich, Carolin and Petkov, Nicolai and Radeva, Petia}, journal={Pattern Recognition}, pages={107330}, year={2020}, publisher={Elsevier}
EgoRoutine
No full textThe EgoRoutine is the first dataset for behaviour characterisation in egocentric photo-streams. 100k images collected by 7 different users. @article{talavera2020topic, title={Topic Modelling for Routine Discovery from Egocentric Photo-streams}, author={Talavera, Estefania and Wuerich, Carolin and Petkov, Nicolai and Radeva, Petia}, journal={Pattern Recognition}, pages={107330}, year={2020}, publisher={Elsevier}
EgoRoutine
No full textThe EgoRoutine is the first dataset for behaviour characterisation in egocentric photo-streams. 100k images collected by 7 different users. @article{talavera2020topic, title={Topic Modelling for Routine Discovery from Egocentric Photo-streams}, author={Talavera, Estefania and Wuerich, Carolin and Petkov, Nicolai and Radeva, Petia}, journal={Pattern Recognition}, pages={107330}, year={2020}, publisher={Elsevier}
EgoRoutine
No full textThe EgoRoutine is the first dataset for behaviour characterisation in egocentric photo-streams. 100k images collected by 7 different users. @article{talavera2020topic, title={Topic Modelling for Routine Discovery from Egocentric Photo-streams}, author={Talavera, Estefania and Wuerich, Carolin and Petkov, Nicolai and Radeva, Petia}, journal={Pattern Recognition}, pages={107330}, year={2020}, publisher={Elsevier}
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