The complex regulation of NIS expression and activity in thyroid and extrathyroidal tissues

The sodium/iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates active iodide transport into the thyroid gland and into several extrathyroidal tissues. NIS-mediated iodide uptake plays a pivotal role in the biosynthesis of thyroid hormones, of which iodide is an essential constituent. For 80 years, radioiodide has been used for the diagnosis and treatment of thyroid cancer, a successful theranostic agent that is extending its use to extrathyroidal malignancies. The purpose of this review is to focus on the most recent findings regarding the mechanisms that regulate NIS both in thyroid and extra-thyroidal tissues. Among other issues, we discuss the different transcriptional regulatory elements that govern NIS transcription in different tissues, the epigenetic modifications that regulate its expression, and the role that miRNAs play in fine-tuning NIS after being transcribed. A review on how hormones, cytokines, and iodide itself regulate NIS is provided. We also review the present stage of understanding NIS dysregulation in cancer, occupied mainly by convergent signaling pathways and by new insights in the route that NIS follows through different subcellular compartments to the plasma membrane. Furthermore, we cover NIS distribution and function in the increasing number of extrathyroidal tissues that express the symporter, as well as the role that NIS plays in tumor progression independently of its transport activity.post-print5810 K

Estudio de iodoproteínas y iodoaminoácidos tiroideos en glándulas humanas patológicas y animales experimentales

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída en 1972.Fac. de MedicinaTRUEProQuestpu

Estudio de iodoproteínas y iodoaminoácidos tiroideos en glándulas humanas patológicas y animales experimentales

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída en 1972.Fac. de MedicinaTRUEProQuestpu

Impaired microRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness.

The global downregulation of microRNAs (miRNAs) is emerging as a common hallmark of cancer. However, the mechanisms underlying this phenomenon are not well known. We identified that the oncogenic miR-146b-5p attenuates miRNA biosynthesis by targeting DICER1 and reducing its expression. DICER1 overexpression inhibited all the miR-146binduced aggressive phenotypes in thyroid cells. Systemic injection of an anti-miR-146b in mice with orthotopic thyroid tumors suppressed tumor growth and recovered DICER1 levels. Notably, DICER1 downregulation promoted proliferation, migration, invasion, and epithelial-mesenchymal transition through miRNA downregulation. Our analysis of The Cancer Genome Atlas revealed a general decrease in DICER1 expression in thyroid cancer that was associated with a worse clinical outcome. Administration of the small-molecule enoxacin to promote DICER1 complex activity reduced tumor aggressiveness both in vitro and in vivo. Overall, our data confirm DICER1 as a tumor suppressor and show that oncogenic miR-146b contributes to its downregulation. Moreover, our results highlight a potential therapeutic application of RNA-based therapies including miRNA inhibitors and restoration of the biogenesis machinery, which may provide treatments for thyroid and other cancers.post-print3221 K

Ras subcellular localization inversely regulates thyroid tumor growth and dissemination

RAS mutations are the second most common genetic alteration in thyroid tumors. However, the extent to which they are associated with the most aggressive phenotypes is still controversial. Regarding their malignancy, the majority of RAS mutant tumors are classified as undetermined, which complicates their clinical management and can lead to undesired under-or overtreatment. Using the chick embryo spontaneous metastasis model, we herein demonstrate that the aggressiveness of HRAS-transformed thyroid cells, as determined by the ability to extravasate and metastasize at distant organs, is orchestrated by HRAS subcellular localization. Remarkably, aggressiveness inversely correlates with tumor size. In this respect, we also show that RAS sitespecific capacity to regulate tumor growth and dissemination is dependent on VEGF-B secretion. Furthermore, we have identified the acyl protein thioesterase APT-1 as a determinant of thyroid tumor growth versus dissemination. We show that alterations in APT-1 expression levels can dramatically affect the behavior of thyroid tumors, based on its role as a regulator of HRAS sublocalization at distinct plasma membrane microdomains. In agreement, APT-1 emerges in thyroid cancer clinical samples as a prognostic factor. As such, APT-1 levels could serve as a biomarker that could help in the stratification of HRAS mutant thyroid tumors based on their aggressiveness.PC lab is supported by grant RTI2018-096658B-100 from the Spanish Ministry of Science (MICIU/AEI/FEDER, UE). Santisteban, Riesco and Crespo Laboratories are supported jointly by grants from Asociación Española Contra el Cancer (AECC; GCB141423113) and CIBERONC from the Instituto de Salud Carlos III (ISCIII). PS acknowledges support from: SAF2016-75531-R (MINECO/FEDER, UE); B2017/BMD-3724 Tironet2 (Comunidad de Madrid) and PID2019-105303RB-I00/AEI/10.13039/501100011033 from Ministerio de Ciencia e Innovación (MICIN). B.C is funded by Retos Jóvenes Investigadores grant SAF2015-73364-JIN (MICIU/AEI/FEDER, UE), a PIE grant from Consejo Superior de Investigaciones Científicas (CSIC)- MICIU and the Ramón y Cajal Research Program (MICIU, RYC2018-024004-I)

Fischer–Tropsch Synthesis Over Zr-Promoted Co/γ-Al2O3 Catalysts

Two Zr-modified alumina supports were synthetized containing the same amount of Zr but a different distribution of this modifier over the alumina surface. These supports, together with the unmodified alumina carrier, were used to prepare three cobalt-based catalysts which were characterized and tested under relevant Fischer–Tropsch conditions. The three catalysts presented very similar porosity and cobalt dispersion. The addition of Zr nor its distribution enhanced the catalyst reducibility. The catalyst activity was superior when using a carrier consisting of large ZrO2 islands over the alumina surface. The use of a carrier with a homogeneous Zr distribution had however, a detrimental effect. Moreover, a faster initial deactivation rate was observed for the Zr-promoted catalysts, fact that may explain this contradictory effect of Zr on activity. Finally, the addition of Zr showed a clear enhancement of the selectivity to long chain hydrocarbons and ethylene, especially when Zr was well dispersed

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate diseaseprogression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumorsenriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differentialexpression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients withrecurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publiclypost-print1,62 M

Pion and photon couplings of N* resonances from scattering on the proton

Results of a relativistic model for pion- and photon-induced reactions on the proton are presented. The model is crossing symmetric and gauge invariant. The nucleon resonances P_11 (1440), P_11 (1710), D_13 (1520), S_11 (1535), S_11 (1650), P_33 (1232), P_33 (1600), S_31 (1620), and D_33 (1700) have been included explicitly in the calculation. Unitarity within the channel space \pi N + \gamma N below the two-pion production threshold has been achieved by using the K-matrix approach. Strong and electromagnetic coupling parameters of the N* resonances have been determined from a fit to the pion-nucleon phase shifts, pion-photoproduction multipoles and Compton-scattering cross sections. The model is shown to describe simultaneously most of the available data. Results for the electric and magnetic polarizabilities of the nucleon are presented.Comment: 12 pages, 3 figures, Revte

Título: Revista de crítica de literatura latinoamericana. Año 43, n. 85 (1º semestre, 2017) : p. [73]-99

Ponencia presentada en el Congreso Internacional "El Inca Garcilaso en Dos Orillas: Conmemorando los 400 Años de su Muerte" que se llevó a cabo los días del 23 al 24 de noviembre de 2016 en la Universidad de AlicanteEstudio que toma como base las cartas del Inca Garcilaso enviadas al Lic. Fernández Franco y el epistolario colectivo de este humanista español, perteneciente al legajo de la colección de la Casa Cadaval, depositado en la Torre do Tombo ("Casa Cadaval, Papeles varios curiosos, PT-TT-CCDV-20", Lisboa)Bibliografía: p. 91-9