Análisis historiográfico y técnico-conservativo de una pintura sobre lienzo peregrina de iconografía carmelitana y tendencia novohispánica

[ES] A lo largo de los siglos XVI y XVII la sociedad europea experimentó un gran cambio socio-cultural y político, a causa de la depresión económica que se produjo como resultado de la contrarreforma. El movimiento político-eclesiástico bajo el papado romano, produjo el nacimiento de las primeras misiones de evangelización, con el afán de unificar y frenar el avance de las nuevas doctrinas protestantes en Europa. Fue entonces cuando se iniciaron los primeros movimientos misioneros especialmente en América, África y Asia, con el fin de expandir la religión católica. Este proceso de evangelización provocó la conquista de América por la monarquía Hispánica estableciendo colonias españolas, llevando consigo nuevas vías de extensión socio cultural y económica. Los territorios colonizados por el Imperio español en América del Norte, América Central y el Caribe fueron referenciados con el término de la ‘Nueva España’ y por paralelismo, las obras ejecutadas por los artistas en estas áreas geográficas, se denominaron pinturas novohispánicas. En este artículo, se desarrolla un estudio histórico, técnico y analítico, de una pintura al óleo sobre lienzo de traza novohispánica del siglo XVIII, donde se representa la imagen de Nuestra Señora del Carmen. La obra se conserva sin tensar en bastidor, enrollada con la pintura hacia su interior alojada en una caja de madera cilíndrica, que permite su transporte y movilidad, de ahí la definición de obra ‘peregrina’. Se analiza también el estado de conservación de la pieza, y las cuestiones vinculadas a su función devocional, con graves desgarros en su soporte y gran cantidad de pérdida matérica del color.[EN] Throughout the 16th and 17th centuries European society experienced a great sociocultural and political change, due to the economic depression that occurred as a result of the counter-reformation. The political-ecclesiastical movement under the Roman papacy produced the birth of the first missions of evangelization, with the desire to unify and slow the advancement of new Protestant doctrines in Europe. It was then that the first missionary movements began especially in America, Africa and Asia in order to expand the Catholic religion. This process of evangelization led to the conquest of America by the Hispanic monarchy by establishing Spanish colonies, carrying with its new avenues of socio-cultural and economic extension. The territories colonized by the Spanish Empire in North America, Central America and the Caribbean were referenced with the term 'New Spain' and by parallelism, the works executed by artists in these geographical areas were called Novohispranic paintings. In this article, a historical, technical and analytical study of an oil painting on canvas of novohisponic trace of the eighteenth century is developed, depicting the image of Our Lady of Carmen. The work is preserved without tensioning in the frame, rolled with the paint inside housed in a cylindrical wooden box, which allows its transport and mobility, hence the definition of 'pilgrim' work. It also analyzes the conservation status of the part, and the issues related to its devotional function, with serious tears in its support and a lot of mattic loss of color.Molina Vañó, Á.; Martín Rey, S. (2020). Análisis historiográfico y técnico-conservativo de una pintura sobre lienzo peregrina de iconografía carmelitana y tendencia novohispánica. Arché. (13 - 14 - 15):157-162. http://hdl.handle.net/10251/15657915716213 - 14 - 1

A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior

Three-dimensional (3D) bioprinted culture systems allow to accurately control microenvironment components and analyze their effects at cellular and tissue levels. The main objective of this study was to identify, quantify and localize the effects of physical-chemical communication signals between tumor cells and the surrounding biomaterial stiffness over time, defining how aggressiveness increases in SK-N-BE(2) neuroblastoma (NB) cell line. Biomimetic hydrogels with SK-N-BE(2) cells, methacrylated gelatin and increasing concentrations of methacrylated alginate (AlgMA 0%, 1% and 2%) were used. Young's modulus was used to define the stiffness of bioprinted hydrogels and NB tumors. Stained sections of paraffin-embedded hydrogels were digitally quantified. Human NB and 1% AlgMA hydrogels presented similar Young´s modulus mean, and orthotopic NB mice tumors were equally similar to 0% and 1% AlgMA hydrogels. Porosity increased over time; cell cluster density decreased over time and with stiffness, and cell cluster occupancy generally increased with time and decreased with stiffness. In addition, cell proliferation, mRNA metabolism and antiapoptotic activity advanced over time and with stiffness. Together, this rheological, optical and digital data show the potential of the 3D in vitro cell model described herein to infer how intercellular space stiffness patterns drive the clinical behavior associated with NB patients

Caracterización molecular de pacientes clínicamente diagnosticados de distrofia muscular de Duchenne/Becker: secuenciación del gen de la distrofina

[ES] Las distrofias musculares de Duchenne y Becker (DMD y DMB) son enfermedades neuromusculares caracterizadas por atrofia y debilidad musculares progresivas, como consecuencia de la degeneración de los músculos esqueléticos, lisos y cardíacos. Estas enfermedades, de herencia recesiva ligada al X, son uno de los tipos de distrofia muscular más prevalentes asociadas a mutaciones en el gen de la distrofina (DMD). Actualmente no hay un tratamiento curativo para estas distrofias musculares, sin embargo existen dos aproximaciones terapéuticas mutación-específicas bajo ensayos clínicos que podrían resultar en potenciales tratamientos: Ataluren y exon-skipping. Estos fármacos van encaminados a restaurar la pauta de lectura en el gen DMD, pero requieren la caracterización de la mutación específica en el gen de la distrofina del paciente. Además las mejoras surgidas en los últimos años han permitido reducir la complejidad de la secuenciación de toda la región codificante del gen DMD. Por ello, el objetivo de este trabajo es, por un lado, conseguir caracterizar molecularmente a los pacientes con diagnóstico clínico de DMD/DMB, mediante un método optimizado para la secuenciación de los 79 exones de este gen; y por otro, evaluar la idoneidad de incluir la secuenciación completa del gen DMD dentro del algoritmo diagnóstico de los pacientes con DMD/DMB.[EN] Duchenne and Becker muscular dystrophies (DMD and BMD) are neuromuscular diseases characterized by progressive muscle wasting and weakness as a result of the degeneration of skeletal, smooth and cardiac muscles. These diseases have X-linked recessive inheritance and are one of the most prevalent muscular dystrophies associated with mutations in the dystrophin gene (DMD). There is currently no cure for these muscular dystrophies, however there are two mutation-specific therapeutic approaches in clinical trials that could lead to potential treatments: Ataluren and exon-skipping. These drugs are intended to restore the open reading frame in the DMD gene, but require the characterization of the specific mutation in the dystrophin gene of the patient. In addition, improvements that have emerged in the last years have reduced the complexity of the sequencing of the whole coding region of the DMD gene. Therefore, the aim of this paper is, first, the molecular characterization of patients with clinical diagnosis of DMD/BMD, using an optimized method for sequencing the 79 exons of this gene, and secondly, to assess the suitability of include the complete sequencing of the DMD gene in the diagnostic algorithm of patients with DMD/BMD.Martín Vañó, S. (2012). Caracterización molecular de pacientes clínicamente diagnosticados de distrofia muscular de Duchenne/Becker: secuenciación del gen de la distrofina. http://hdl.handle.net/10251/27221Archivo delegad

Intra-Tumour Genetic Heterogeneity and Prognosis in High-Risk Neuroblastoma

Spatial ITH is defined by genomic and biological variations within a tumour acquired by tumour cell evolution under diverse microenvironments, and its role in NB patient prognosis is understudied. In this work, we applied pangenomic techniques to detect chromosomal aberrations in at least two different areas of each tumour and/or in simultaneously obtained solid and liquid biopsies, detecting ITH in the genomic profile of almost 40% of HR-NB. ITH was better detected when comparing one or more tumour pieces and liquid biopsy (50%) than between different tumour pieces (21%). Interestingly, we found that patients with ITH analysed by pangenomic techniques had a significantly better survival rate that those with non-heterogeneous tumours, especially in cases without MYCN amplification. Moreover, all patients in the studied cohort with high ITH (defined as 50% or more genomic aberration differences between areas of a tumour or simultaneously obtained samples) survived after 48 months. These results clearly support analysing at least two solid tumour areas (separately or mixed) and liquid samples to provide more accurate genomic diagnosis, prognosis and therapy options in HR-NB

Digital Image Analysis Applied to Tumor Cell Proliferation, Aggressiveness, and Migration-Related Protein Synthesis in Neuroblastoma 3D Models

Patient-derived cancer 3D models are a promising tool that will revolutionize personalized cancer therapy but that require previous knowledge of optimal cell growth conditions and the most advantageous parameters to evaluate biomimetic relevance and monitor therapy efficacy. This study aims to establish general guidelines on 3D model characterization phenomena, focusing on neuroblastoma. We generated gelatin-based scaffolds with different stiffness and performed SK-N-BE(2) and SH-SY5Y aggressive neuroblastoma cell cultures, also performing co-cultures with mouse stromal Schwann cell line (SW10). Model characterization by digital image analysis at different time points revealed that cell proliferation, vitronectin production, and migration-related gene expression depend on growing conditions and are specific to the tumor cell line. Morphometric data show that 3D in vitro models can help generate optimal patient-derived cancer models, by creating, identifying, and choosing patterns of clinically relevant artificial microenvironments to predict patient tumor cell behavior and therapeutic responses

Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma

Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to specifically target tumor cells within these altered matrices by employing nanomedicine and combination therapy. Loading the conventional cytotoxic drug etoposide into nanoparticles significantly increased its efficacy in neuroblastoma cells. We noted high synergy between etoposide and cilengitide, a high-affinity cyclic pentapeptide αv integrin antagonist. The results of this study highlight the need to characterize cell-extracellular matrix interactions, to improve patient care in high-risk neuroblastoma.This work was supported by grants from ISCIII and ERDF [PI17/01558] and [PI20/01107]; CIBERONC [contract CB16/12/00484]; Asociación Española contra el Cáncer [FAECC2015/006]; NEN Association [Nico contra el cancer infantil 2017 – PVR00157] and the Neuroblastoma Foundation [PVR00166]