Tumor de células granulares de localización atípica

El Tumor de células granulares es una neoplasia infrecuente, generalmente benigna, que suele afectar cara y cuello. Aparece entre la segunda y la sexta década, más frecuentemente en la raza negra y en mujeres. El 25% de los casos presenta lesiones múltiples. El único tratamiento es quirúrgico. Un varón de 17 años presentó una lesión nodular única epitroclear en el codo derecho. Se realizó una escisión amplia y el resultado anatomopatológico fue un tumor de células granulares. Tras un seguimiento de seis meses no hay evidencia de recidiva. La patogénesis debe ser claramente establecida, aunque la literatura sostiene la hipótesis de que tiene su origen en las células de Schwann. Los autores subrayan la peculiaridad de la localización epitroclear y discuten la clasificación, fisiopatología y el tratamiento del tumor con una revisión de la literatura. (MÉD.UIS. 2011;24(3):283-6).Palabras clave: Cáncer. Tumor de células granulares. Inmunohistoquímica.Granular cell tumor in unusual location.Granular cell tumor is an infrequent neoplasm, benign in most of the cases, that usually affects head and neck. It develops between the second and sixth decades of life, more frequently among women and black people. 25% of the cases occur as multiple lesions. The only treatment is surgery. A 17- year old male presented a nodular, single and firm epithroclear lesion in his right elbow. A wide surgical excision was performed and the final pathologic diagnosis was granular cell tumor. During follow-up of six months there is no evidence of tumour recurrence. The pathogenesis of the tumor has still to be clearly established, although literature sustains the hypothesis that it has origin in the Schwann´s cells. The authors underscore the peculiarity of the epithroclear localization and discuss the classification, pathophysiology and the treatment of Abrikossoff´s tumor through a review of the literature. (MÉD.UIS. 2011;24(3):283-6).Key words: Cancer. Granular cell tumor. Inmunohistochemistry

Characterisation of resistance mechanisms developed by basal cell carcinoma cells in response to repeated cycles of photodynamic therapy

photodynamic therapy (pDt) with methyl-aminolevulinate acid (MAL-pDt) is being used for the treatment of Basal cell carcinoma (BCC), but recurrences have been reported. In this work, we have evaluated resistance mechanisms to MAL-pDt developed by three BCC cell lines (AsZ, BsZ and CsZ), derived from mice on a ptch+/− background and with or without p53 expression, subjected to 10 cycles of PDT (10thG). the resistant populations showed mesenchymal-like structure and diminished proliferative capacity and size compared to the parental (p) cells. the resistance was dependent on the production of the endogenous photosensitiser protoporphyrin IX in the CsZ cell line and on its cellular localisation in AsZ and BsZ cells. Moreover, resistant cells expressing the p53 gene presented lower proliferation rate and increased expression levels of N-cadherin and Gsk3β (a component of the Wnt/β-catenin pathway) than P cells. In contrast, 10thG cells lacking the p53 gene showed lower levels of expression of Gsk3β in the cytoplasm and of e-cadherin and β-catenin in the membrane. In addition, resistant cells presented higher tumorigenic ability in immunosuppressed mice. Altogether, these results shed light on resistance mechanisms of BCC to pDt and may help to improve the use of this therapeutic approac

Understanding the retreat of the Jurassic Cantabrian coast (N. Spain): comprehensive monitoring and 4D evolution model of the Tazones Lighthouse landslide

Forecasting coastal dynamics and sea cliff retreat under different sea level rise scenarios requires a good understanding of the conditioning factors and their relative contribution to cliff stability. The so-called Jurassic Cantabrian Coast extends along 76 km of the coastline of the Asturias region (N Spain) and is well-known worldwide due to its paleontological heritage, in particular the presence of dinosaur remains and footprints. The abundance of stratigraphic, paleontological and tectonic studies contrasts with the scarcity of studies focused on the stability of this rocky coastline where cliffs predominate, sometimes exceeding 120 m in height. In fact, evidence of current and recent instability processes can be observed along the entire coastline. In this regard, continuous monitoring is crucial to understand ongoing instabilities in rocky coastlines, as in these settings some instabilities might initiate as slow movements that induce subtle topographic changes whose detection from either satellite or aerial imagery is problematic due to the spatial and temporal resolutions.This research is part of 1) the “COSINES” Project [CGL2017-83909-R], Call 2017 for RETOS Projects funded by the Spanish Economy, Industry and Competitiveness Ministry-Ministerio de Economía, Industria y Competitividad (MINECO), the Spanish Research Agency-Agencia Estatal de Investigación (AEI) and the European Regional Development Found (FEDER) and 2) the GEOCANCOSTA research group, supported by the Asturian Regional Government (Spain) [grant number GRUPIN-IDI-2018-184]

Minimally invasive system to reliably characterize ventricular electrophysiology from living donors

Cardiac tissue slices preserve the heterogeneous structure and multicellularity of the myocardium and allow its functional characterization. However, access to human ventricular samples is scarce. We aim to demonstrate that slices from small transmural core biopsies collected from living donors during routine cardiac surgery preserve structural and functional properties of larger myocardial specimens, allowing accurate electrophysiological characterization. In pigs, we compared left ventricular transmural core biopsies with transmural tissue blocks from the same ventricular region. In humans, we analyzed transmural biopsies and papillary muscles from living donors. All tissues were vibratomesliced. By histological analysis of the transmural biopsies, we showed that tissue architecture and cellular organization were preserved. Enzymatic and vital staining methods verifed viability. Optically mapped transmembrane potentials confrmed that action potential duration and morphology were similar in pig biopsies and tissue blocks. Action potential morphology and duration in human biopsies and papillary muscles agreed with published ranges. In both pigs and humans, responses to increasing pacing frequencies and β-adrenergic stimulation were similar in transmural biopsies and larger tissues. We show that it is possible to successfully collect and characterize tissue slices from human myocardial biopsies routinely extracted from living donors, whose behavior mimics that of larger myocardial preparations both structurally and electrophysiologically.Fil: Oliván Viguera, Aida. Universidad de Zaragoza; EspañaFil: Pérez Zabalza, María. Universidad de Zaragoza; EspañaFil: García Mendívil, Laura. Universidad de Zaragoza; EspañaFil: Mountris, Konstantinos A.. Universidad de Zaragoza; EspañaFil: Orós Rodrigo, Sofía. Universidad de Zaragoza; EspañaFil: Ramos Marquès, Estel. Universidad de Zaragoza; EspañaFil: Vallejo Gil, José María. University Hospital Miguel Servet; EspañaFil: Fresneda Roldán, Pedro Carlos. University Hospital Miguel Servet; EspañaFil: Fañanás Mastral, Javier. University Hospital Miguel Servet; EspañaFil: Vázquez Sancho, Manuel. University Hospital Miguel Servet; EspañaFil: Matamala Adell, Marta. University Hospital Miguel Servet; EspañaFil: Sorribas Berjón, Fernando. University Hospital Miguel Servet; EspañaFil: Bellido Morales, Javier André. University Hospital Miguel Servet; EspañaFil: Mancebón Sierra, Francisco Javier. University Hospital Miguel Servet; EspañaFil: Vaca Núñez, Alexánder Sebastián. University Hospital Miguel Servet; EspañaFil: Ballester Cuenca, Carlos. University Hospital Miguel Servet; EspañaFil: Marigil, Miguel Ángel. Hospital San Jorge; EspañaFil: Pastor, Cristina. Aragón Institute of Health Sciences; EspañaFil: Ordovás, Laura. Aragón Agency for Research and Development; España. Universidad de Zaragoza; EspañaFil: Köhler, Ralf. Aragón Institute of Health Sciences; España. Aragón Agency for Research and Development; EspañaFil: Diez, Emiliano Raúl. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Fisiología Humana Normal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pueyo, Esther. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina; España. Universidad de Zaragoza; Españ

Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System

Objective In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. Methods It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. Results The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. Conclusion Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)

Tumor de células granulares de localización atípica

El Tumor de células granulares es una neoplasia infrecuente, generalmente benigna, que suele afectar cara y cuello. Aparece entre la segunda y la sexta década, más frecuentemente en la raza negra y en mujeres. El 25% de los casos presenta lesiones múltiples. El único tratamiento es quirúrgico. Un varón de 17 años presentó una lesión nodular única epitroclear en el codo derecho. Se realizó una escisión amplia y el resultado anatomopatológico fue un tumor de células granulares. Tras un seguimiento de seis meses no hay evidencia de recidiva. La patogénesis debe ser claramente establecida, aunque la literatura sostiene la hipótesis de que tiene su origen en las células de Schwann. Los autores subrayan la peculiaridad de la localización epitroclear y discuten la clasificación, fisiopatología y el tratamiento del tumor con una revisión de la literatura. (MÉD.UIS. 2011;24(3):283-6).Granular cell tumor is an infrequent neoplasm, benign in most of the cases, that usually affects head and neck. It develops between the second and sixth decades of life, more frequently among women and black people. 25% of the cases occur as multiple lesions. The only treatment is surgery. A 17- year old male presented a nodular, single and firm epithroclear lesion in his right elbow. A wide surgical excision was performed and the final pathologic diagnosis was granular cell tumor. During follow-up of six months there is no evidence of tumour recurrence. The pathogenesis of the tumor has still to be clearly established, although literature sustains the hypothesis that it has origin in the Schwann´s cells. The authors underscore the peculiarity of the epithroclear localization and discuss the classification, pathophysiology and the treatment of Abrikossoff´s tumor through a review of the literature. (MÉD.UIS. 2011;24(3):283-6)

Development of a DIPG Orthotopic Model in Mice Using an Implantable Guide-Screw System

Objective In this work we set to develop and to validate a new in vivo frameless orthotopic Diffuse Intrinsic Pontine Glioma (DIPG) model based in the implantation of a guide-screw system. Methods It consisted of a guide-screw also called bolt, a Hamilton syringe with a 26-gauge needle and an insulin-like 15-gauge needle. The guide screw is 2.6 mm in length and harbors a 0.5 mm central hole which accepts the needle of the Hamilton syringe avoiding a theoretical displacement during insertion. The guide-screw is fixed on the mouse skull according to the coordinates: 1mm right to and 0.8 mm posterior to lambda. To reach the pons the Hamilton syringe is adjusted to a 6.5 mm depth using a cuff that serves as a stopper. This system allows delivering not only cells but also any kind of intratumoral chemotherapy, antibodies or gene/viral therapies. Results The guide-screw was successfully implanted in 10 immunodeficient mice and the animals were inoculated with DIPG human cell lines during the same anesthetic period. All the mice developed severe neurologic symptoms and had a median overall survival of 95 days ranging the time of death from 81 to 116 days. Histopathological analysis confirmed tumor into the pons in all animals confirming the validity of this model. Conclusion Here we presented a reproducible and frameless DIPG model that allows for rapid evaluation of tumorigenicity and efficacy of chemotherapeutic or gene therapy products delivered intratumorally to the pons

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)