12 research outputs found
The sacral chordoma margin
[Objective]: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.
[Background]: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.
[Methods]: A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.
[Results]: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.
[Conclusion]: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients
Parque Sanitario Tecnópolis: aportes desde el Trabajo Social para un acompañamiento integralen tiempos de pandemia
Fil: Rabasa Rucki, Carolina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Carrera de Trabajo Social, Argentina.Fil: Ramírez, Marisa. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Carrera de Trabajo Social, Argentina.Fil: Rojas, Marcela. Universidad de Morón, Argentina.Fil: di Pasquale, Sebastián. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Carrera de Trabajo Social, Argentina.Fil: Barone, Diego. Instituto Superior Fasta Inmaculada Concepción, Argentina.Fil: Cordoba, Nadia. Universidad Nacional de Moreno, Argentina.Fil: Camps, Facundo. Instituto Superior de Ciencias Humanas y Sociales, Argentina.Fil: Carrizo, Aldana. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Carrera de Trabajo Social, Argentina.Fil: Campagnucci, Lidia. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Carrera de Trabajo Social, Argentina.En el marco de la pandemia se ha constituido el Parque Sanitario Tecnópolis, el mismo es parte de las políticas públicas que se despliegan para enfrentar el COVID-19. Tiene como objetivo poder acoger a aquellas personas contagiadas que no disponen de las condiciones necesarias para cumplir el aislamiento en sus lugares de albergue y de esta manera evitar el contagio de otras/os. Si bien la dirección está bajo la órbita del Ministerio de Salud de la Provincia de Buenos Aires, se incorporó al dispositivo una fuerte mirada social en pos de abordar la complejidad e integralidad de los destinatarios a asistir que rompe en cierto punto con una mirada hegemónica centrada en lo biológico instalada en algunas instituciones sanitarias. De esta manera se han incorporado Trabajadoras/es Sociales en diferentes roles del dispositivo, participando en distintos espacios interdisciplinarios junto a médicas/os, enfermeras/os y psicólogas/os. El presente artículo narra las características de este centro de aislamiento, describe los aportes que desde la disciplina del Trabajo Social se han realizado, cuenta alguna de las intervenciones desplegadas, enumera ciertos desafíos que se afrontan desde la política pública para enfrentar la pandemia y por ultimo da cuenta de algunas reflexiones preliminares en torno al aporte que se puede hacer desde el colectivo del Trabajo Social al funcionamiento del Parque Sanitario y desde ahí a diferentes instituciones y procesos que buscan intervenir sobre la problemática de salud
Abstract B41: Withaferin A promotes ROS-mediated differentiation of neuroblastoma
Abstract
Background: Neuroblastoma (NB), the most common extra-cranial solid tumor in children, originates from the precursor neuroblasts of the sympathetic nervous system. NB accounts for approximately 7-10% of childhood cancers and 15% of childhood cancer death. Despite an aggressive treatment regimen, the 5-year survival for high risk NB remains less than 50%. The differentiation of NB cells into mature cells represents a promising strategy for NB therapy. Currently, retinoids are the most commonly used differentiating agents. However, their use can be limited due to intrinsic or acquired resistance, as well as toxicity. We sought to evaluate the potential of the natural product withaferin A (WA), a steroidal lactone derived from the medicinal plant Withania somnifera, to induce NB cell differentiation.
Methods: For differentiation studies NB cell lines (NB1691, SMS-KCNR, SH-SY5Y and the primary cell line SVBM15) were exposed to WA (100-500nM) for 7-10 days and evaluated by light microscopy, immunocytochemistry and western blot analysis. NB stem-like cell lines were generated by culturing NB1691 and SVBM15 cells in neurosphere media. To determine the IC50 (concentration needed to reduce viability by 50%), NB stem-like cell lines were exposed to increasing concentrations of WA and viability was assessed at 72 hours using MTS assay. Reactive oxygen species (ROS) were detected using CM-H2DFDA and ROS induction was inhibited with N-acetyl-L- Cysteine (NAC). To determine WA effect on neurosphere formation, NB cells were plated in 96-well plates at 50 cells/well. Cells were grown in increasing concentrations of WA and spheres were counted at 14 days.
Results: WA promoted morphologic alterations (neurite outgrowth) and growth inhibition in a dose dependent manner. Immunocytochemistry and western blot analysis indicated an increase in neuronal markers including neurofilament, β-tubulin and MAP2, as well as a decrease in the stem cell markers BMi-1 and musashi. WA promoted ROS induction, which could be prevented with NAC pretreatment. NAC prevented WA-induced morphological changes and inhibited WA-induced changes in stem cell and differentiation marker expression. WA induced NB stem-like cell death in a dose dependent manner (IC50 of NB1691=1.05 μM; SVBM15=1.06 μM), and significantly inhibited neurosphere formation at concentrations as low as 50nM, which did not exhibit cytotoxicity in regular cell culture conditions.
Conclusion: Withania somnifera has been used for centuries and is commonly used in ayurvedic medicine. WA has been shown to affect multiple pathways important for cancer progression and induce anti-cancer effects in breast, prostate and pancreatic cancers. Our data indicates that WA induces NB stem-like cell death, and promotes ROS-mediated NB cell differentiation. Differentiation therapy aims at reducing the risk of the tumor regrowth following high-dose chemotherapy and stem cell transplant in patients classified as high-risk. WA holds great promise as a novel alternative NB treatment strategy for children with persistent minimal residual disease.
Citation Format: Gregor A. Rodriguez, Claudia P. Zapata, Anthony Sanchez, Nicolas A. De Cordoba, Beatriz E. Hawkins, Nadia G. Myrthil, Sarah A. Samuels, Amelia Bahamonde, Steven Vanni, Regina M. Graham. Withaferin A promotes ROS-mediated differentiation of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B41.</jats:p
Sedimentary analysis and magnetic properties from the highly variable Lake Anónima, Vega Island
During the summer Lake Anónima experiences important changes in salinity and lake level fluctuations. Physicochemical data and field observations indicate that evaporative processes are dominant and that the water inflow is mainly provided by snow meltwater and streams. A multiproxy analysis of data from lake bottom sediments suggests that the main surface stream located south-west of the lake controls the clastic input and the spatial variation of sediment composition. Through an integrated analysis (magnetic, X-ray diffraction and Fourier Transform Infrared Spectroscopy studies) magnetite and greigite minerals were identified in these lake sediments. Such ferrimagnetic minerals have ultra-fine grain sizes (<0.1 μm). Magnetic parameters and non-magnetic variables analysed by multivariate statistics reveal significant differences between silt facies (e.g. mass-specific susceptibility χ = 109.6 × 10-8m3kg-1, remanent coercivity Hcr = 49.2mT and total organic carbon (TOC) = 1.11%) and sand facies (e.g. χ = 82.1 × 10-8m3kg-1, Hcr = 44.7mT and TOC = 0.70%), and four recent depositional sub-environments were identified and characterized in Lake Anónima. This multiparameter analysis contributes to the understanding of present-day lacustrine dynamic and sedimentary processes. Lake Anónima may provide a useful analogue for the interpretation of other lacustrine basins in the Antarctic region.Fil: Chaparro, Marcos Adrián Eduardo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Matemática; ArgentinaFil: Chaparro, Mauro Alejandro Eduardo. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Matemática; ArgentinaFil: Cordoba, Francisco Elizalde. Universidad Nacional de Jujuy; ArgentinaFil: Lecomte, Karina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Gargiulo, José Daniel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Barrios AM. Universidad de Granada; EspañaFil: Uran, Gimena Mariel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: Manograsso Czalbowski, Nadia. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Lavat, Araceli Elisabet. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Böhnel, Harald N.. Universidad Nacional Autónoma de México; Méxic
Magnetic parameters in paleolimnologicalstudies in Antarctica
En esta contribución se describen las distintas técnicas y mediciones magnéticas utilizadas en Magnetismo Ambiental y Paleomagnetismo. Tales mediciones ofrecen útiles indicadores para realizar estudios relacionados con cambios climáticos y ambientales, así como herramientas de datación. Si bien es ampliamente conocida la utilidad de la susceptibilidad magnética, se discute el potencial y necesidad del uso de parámetros adicionales obtenidos a partir de mediciones de magnetizaciones remanentes (natural, anhistérica e isotérmica), histéresis magnética y estudios termomagnéticos.Se presentan resultados magnéticos obtenidos en sedimentos lacustres del Archipiélago James Ross (NE de la Península Antártica). Se complementa con estudios sedimentológicos, hidroquímicos, geoquímicos y de estadística multivariada, pero se pone énfasis en los parámetros magnéticos y su relación con los distintos procesos que ocurren en los sistemas lacustres antárticos. Se analiza además el uso de las paleointensidades relativas como herramienta de datación en lagunas antárticas.Fil: Chaparro, Marcos Adrián Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Gargiulo, José Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones En Física E Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Iruzun, María A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones En Física E Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Chaparro, Mauro Alejandro Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones En Física E Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Lecomte, Karina Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Ciencias de la Tierra; ArgentinaFil: Böhnel, Harald N.. Universidad Nacional Autonoma de Mexico. Centro de Geociencias; MéxicoFil: Cordoba, Francisco Elizalde. Centro de Investigación y Transferencia de Jujuy. Instituto de Geología y Minería; ArgentinaFil: Vignoni, Paula A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Ciencias de la Tierra; ArgentinaFil: Manograsso Czalbowski, Nadia T.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Lirio, Juan M.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Nowaczyk, Norbert. GeoForschungsZentrum Potsdam; AlemaniaFil: Sinito, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones En Física E Ingeniería del Centro de la Provincia de Buenos Aires; Argentin
Mediterranean dietary patterns and prospective weight change in participants of the EPIC-PANACEA project
Background: There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity. Objective: We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity. Design: We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression. Results: Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of 0.16 kg (95% CI: 0.24, 0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain. Conclusion: This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity. Am J Clin Nutr 2010;92:912-21
Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study
© 2020 Elsevier Ltd. All rights reserved.Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.
Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261.
Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups.
Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.info:eu-repo/semantics/publishedVersio