Manejo preoperatorio del paciente con cáncer de esófago

Introducción: El cáncer de esófago ha sufrido un aumento en su prevalencia. Su baja tasa de supervivencia, así como la agresividad de la intervención quirúrgica necesaria para su tratamiento y sus amplia morbimortalidad y repercusión en la calidad de vida de los paciente al ser diagnosticado en estadios avanzados, se traducen en la necesidad de desarrollar un manejo multimodal de estos pacientes. Su objetivo sería prepararlos preoperatoriamente con el fin de disminuir el número de complicaciones postoperatorias y mejorar su calidad de vida, teniendo en cuenta también el amplio gasto sanitario que suponen. Material y métodos: Se realizó una revisión sistemática de varios artículos en relación con el tema, dividiendo el manejo preoperatorio de estos pacientes en 7 partes (soporte nutricional, apoyo psicológico, fisioterapia respiratoria, tabaco, higiene dental, profilaxis antibiótica y antitrombótica). Se realizó una preselección basada en los criterios de inclusión: revisiones bibliográficas, meta análisis, ensayos controlados aleatorizados y ensayos clínicos, de los últimos diez años. También se consultaron tratados médicos. Se revisaron un total de 35 artículos. Resultados: Varios de estos puntos han demostrado disminuir la morbimortalidad de los pacientes aumentando además su calidad de vida. Entre ellos están la profilaxis antibiótica y antitrombótica, el abandono del hábito tabáquico, la higiene dental y la fisioterapia respiratoria. El soporte nutricional sigue estando en controversia, aunque la disminución de peso > 10% de forma preoperatoria, junto con la malnutrición asociada, han demostrado aumentar las complicaciones postoperatorias, empeorando el pronóstico. Conclusiones: un protocolo de actuación multimodal en el manejo preoperatorio del cáncer de esófago es necesario y supondría una mejora en los resultados de su tratamiento. Debe constar de varias partes, siendo individualizado y explicado al paciente. Los protocolos Fast track y la cirugía mínimamente invasiva deberán seguir extendiéndose, ya que han demostrado una mejoría de la morbilidad y la calidad de vida del paciente con cáncer de esófago que se somete a cirugí

Basement membrane-rich Organoids with functional human blood vessels are permissive niches for human breast cancer metastasis

Metastasic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention

Digital-Analog Quantum Simulations Using The Cross-Resonance Effect

Digital-analog quantum computation aims to reduce the currently infeasible resource requirements needed for near-term quantum information processing by replacing sequences of one- and two-qubit gates with a unitary transformation generated by the systems' underlying Hamiltonian. Inspired by this paradigm, we consider superconducting architectures and extend the cross-resonance effect, up to first order in perturbation theory, from a two-qubit interaction to an analog Hamiltonian acting on 1D chains and 2D square lattices which, in an appropriate reference frame, results in a purely two-local Hamiltonian. By augmenting the analog Hamiltonian dynamics with single-qubit gates we show how one may generate a larger variety of distinct analog Hamiltonians. We then synthesize unitary sequences, in which we toggle between the various analog Hamiltonians as needed, simulating the dynamics of Ising, $XY$, and Heisenberg spin models. Our dynamics simulations are Trotter error-free for the Ising and $XY$ models in 1D. We also show that the Trotter errors for 2D $XY$ and 1D Heisenberg chains are reduced, with respect to a digital decomposition, by a constant factor. In order to realize these important near-term speedups, we discuss the practical considerations needed to accurately characterize and calibrate our analog Hamiltonians for use in quantum simulations. We conclude with a discussion of how the Hamiltonian toggling techniques could be extended to derive new analog Hamiltonians which may be of use in more complex digital-analog quantum simulations for various models of interacting spins

Un paseo por el Jurásico de la provincia de Guadalajara entre Pelegrina y Fuentelsaz

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEMinisterio de Educación y Ciencia. Españapu

A novel lipase-catalyzed method for preparing ELR-based bioconjugates

Producción CientíficaHerein we present a novel one-pot method for the chemical modification of elastin-like recombinamers (ELRs) in a mild and efficient manner involving enzymatic catalysis with Candida antarctica lipase B. The introduction of different functionalities into such ELRs could open up new possibilities for the development of advanced biomaterials for regenerative medicine and, specifically, for controlled drug delivery given their additional ability to respond to stimuli other than pH or temperature, such as glucose concentration or electromagnetic radiation. Candida antarctica lipase B immobilized on a macroporous acrylic resin (Novozym 435) was used to enzymatically couple different aminated substrates to a recombinamer containing carboxylic groups along its amino acid chain by way of an amidation reaction. A preliminary study of the kinetics of this amidation in response to different reaction conditions, such as solvent, temperature or reagent ratio, was carried out using a phenylazobenzene derivative (azo-NH2) as a model. The optimal amidation conditions were used to couple other amine reagents, such as phenylboronic acid (FB-NH2) or polyethylene glycol (PEG-NH2), thus allowing us to obtain photoresponsive, glucose-responsive or PEGylated ELRs that could potentially be useful as sensors in devices for controlled drug delivery.2019-11-112019-11-11European Social Fund (ESF) and European Regional Development Fund (ERDF)Comisión Europea (proyectos NMP-2014-646075, HEALTH-F4-2011-278557, PITN-GA-2012-317306 y MSCA-ITN-2014-642687),Ministerio de Economía, Industria y Competitividad (Projects MAT2015-68901-R, MAT2016-79435-R and MAT2016-78903-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA244U13 y VA313U14)CIBER-BBN, Instituto de Salud Carlos III a través de la Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Novozymes

The paleobotany: a preferred tool on the Earth Sciences Teaching.

Los restos vegetales constituyen unos documentos de origen biótico muy interesantes ya que tienen un registro fósil muy amplio, desde los ambientes marinos del Precámbrico llegando hasta la actualidad. Los plantas fósiles son de un enorme valor para conocer la historia de la Vida en la Tierra lo más completa posible. El binomio animales-plantas no es posible separarlo en las actividades didácticas de las Ciencias de la Tierra si se pretende una imagen real y coherente de cada paso en la historia de nuestro Planeta.The plant remains are a very interesting biotic document owing to the wide fossil record since the Precambrien time until now alowing to know the live history in the earth. The animals-plant relationship is necessary for have a true image of the past times and consequenly is a very important tool on the educational activities in earth sciences.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis

SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified via spatial proteomics as being upregulated in highly metastatic-to-liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly metastatic KM12C CRC cells. Here, we aimed to analyze SPRYD7’s role in CRC via functional proteomics. Through immunohistochemistry, the overexpression of SPRYD7 was observed to be associated with the poor survival of CRC patients and with an aggressive and metastatic phenotype. Stable SPRYD7 overexpression was performed in KM12C and SW480 poorly metastatic CRC cells and in their isogenic highly metastatic-to-liver-KM12SM-and-to-lymph-nodes SW620 CRC cells, respectively. Upon upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in the invasion and migration of CRC cells and in liver homing and tumor growth. Additionally, transient siRNA SPRYD7 silencing allowed us to confirm in vitro functional results. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated via 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated with the stable overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated with CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance in identifying novel therapeutic targets for advanced CRC

Supercritical CO2 and subcritical water technologies for the production of bioactive extracts from sardine (Sardina pilchardus) waste

The valorization of sardine (Sardina pilchardus) waste (SW) from a canning facility has been investigated within a biorefining approach. Sequential fractionation of SW into its constituents has been carried out using green solvents such as supercritical carbon dioxide (SCCO2) and subcritical water (sCW). The lipid fraction has been isolated through supercritical fluid extraction (SFE) with SCCO2 at 250 bar and 40 °C, yielding 20.3 ± 0.2 g oil/100 g SW with up to 17.2 %wt. omega-3 polyunsaturated fatty acids (PUFAs). Aiming at the protein fraction, sCW extraction/hydrolysis has been carried out at different temperatures (90, 140, 190 and 250 °C), using both SW and defatted sardine waste (DSW) from SFE experiments. Previous defatting increased protein recovery and purity. Bioactive properties of the fish protein hydrolysates (FPHs) obtained were affected by the extraction temperature. The highest antioxidant activity and in vitro antiproliferative effect were found in the extracts obtained at 250 °C.FCT/MCTES (UIDB/QUI/50006/2020), and Fundação para a Ciência e a Tecnologia through project PTDC/ASP-PES/28399/2017 and grants IF/01146/2015 and SFRH/BD/116002/201

Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis

Metastasis is the primary cause of colorectal cancer (CRC) death. The liver and lung, besides adjacent lymph nodes, are the most common sites of metastasis. Here, we aimed to study the lymph nodes, liver, and lung CRC metastasis by quantitative spatial proteomics analysis using CRC cell-based models that recapitulate these metastases. The isogenic KM12 cell system composed of the non-metastatic KM12C cells, liver metastatic KM12SM cells, and liver and lung metastatic KM12L4a cells, and the isogenic non-metastatic SW480 and lymph nodes metastatic SW620 cells, were used. Cells were fractionated to study by proteomics five subcellular fractions corresponding to cytoplasm, membrane, nucleus, chromatin-bound proteins, and cytoskeletal proteins, and the secretome. Trypsin digested extracts were labeled with TMT 11-plex and fractionated prior to proteomics analysis on a Q Exactive. We provide data on protein abundance and localization of 4710 proteins in their different subcellular fractions, depicting dysregulation of proteins in abundance and/or localization in the most common sites of CRC metastasis. After bioinformatics, alterations in abundance and localization for selected proteins from diverse subcellular localizations were validated via WB, IF, IHC, and ELISA using CRC cells, patient tissues, and plasma samples. Results supported the relevance of the proteomics results in an actual CRC scenario. It was particularly relevant that the measurement of GLG1 in plasma showed diagnostic ability of advanced stages of the disease, and that the mislocalization of MUC5AC and BAIAP2 in the nucleus and membrane, respectively, was significantly associated with poor prognosis of CRC patients. Our results demonstrate that the analysis of cell extracts dilutes protein alterations in abundance in specific localizations that might only be observed studying specific subcellular fractions, as here observed for BAIAP2, GLG1, PHYHIPL, TNFRSF10A, or CDKN2AIP, which are interesting proteins that should be further analyzed in CRC metastasis.This research was funded by the Instituto de Salud Carlos III (ISCIII) through the PI20CIII/00019 grants from the AES-ISCIII program to R.B., co-financed by the European Development Regional Fund “A way to achieve Europe” (FEDER). J. Hofkens. acknowledges financial support from the Research Foundation–Flanders (FWO, grant No. ZW15_09-G0H6316N), the Flemish government through long-term structural funding Methusalem (CASAS2, Meth/15/04), and the MPI as MPI fellow. S.R. acknowledges the financial support of the KU Leuven through the internal C1 funding (KU Leuven (C14/16/053)). G.S.-F. is the recipient of a predoctoral contract (grant number 1193818N) supported by The Research Foundation–Flanders (FWO). The FPU predoctoral contract to A.M.-C. is supported by the Spanish Ministerio de Educación, Cultura y Deporte.S