Reactive oxygen species (ROS) production in HepG2 cancer cell line through the application of localized alternating magnetic field

This research work is supported by Ministerio de Economia y Competitividad (CGL2016-76723 project), Ramon y Cajal programme (RYC-2014-16901), Junta de Andalucia. Programa Operativo FEDER 2014-2020. (A1-FQM-341-UGR18, C-FQM-497-UGR18, A-BIO-376-UGR18). This research was also aided by the Andalusian regional government (CTS-236). Alberto Sola-Leyva holds a Formacion de Doctores 2018 grant (ref. PRE2018-085440) from the Ministerio de Ciencia, Innovacion y Universidades (Spain). Ylenia Jabalera wants to acknowledge a FPU2016 grant (ref. FPU16_04580) from the Ministerio de Educacion, Ciencia y Deporte y Competitividad (Spain) and Unidad Cientifica de Excelencia UCE-PP2016-05 of the University of Granada. This study is part of a PhD Thesis conducted at the University of Granada, Spain. Finally, thanks go to the CIC personnel of the University of Granada for technical assistance in the TEM.Recent studies have shown the potential of magnetic hyperthermia in cancer treatments. However, the underlying mechanisms involved have not been yet fully described. In particular, the cell death related to magnetic hyperthermia observed in cultures incubated with low concentration of magnetic nanoparticles and under a low intensity alternating magnetic field, in which a macroscopic temperature rise is not observed, is still not understood. In the present study, we investigate the production of intracellular Reactive Oxygen Species (ROS) as a mechanism to induce cell death under these conditions. In this study, the production and influence of ROS on the viability of HepG2 human hepatoma cells (used as a model cell line) are analyzed under the application of variable magnetic fields using hyperthermia agents, such as biomimetic magnetic nanoparticles (BMNPs) mediated by magnetosome MamC protein fromMagnetococcus marinusMC-1. The results show that intracellular ROS production increases up to similar to 90% following upon the exposure of AMF to HepG2 cells containing BMNPs, which could determine the loss of cell viability (up to similar to 40% reduction) without a significant rise in temperature. Such ROS production is linked to mitochondrial dysfunction caused by the application of AMF to cells containing BMNPs.Spanish Government CGL2016-76723Spanish Government RYC-2014-16901Junta de AndaluciaPrograma Operativo FEDER 2014-2020 A1-FQM-341-UGR18 C-FQM-497-UGR18 A-BIO-376-UGR18Andalusian regional government CTS-236Ministerio de Ciencia, Innovacion y Universidades (Spain) PRE2018-085440Ministerio de Educacion, Ciencia y Deporte y Competitividad (Spain) FPU16_04580Unidad Cientifica de Excelencia of the University of Granada UCE-PP2016-0

Plant-Derived Bioactive Compounds for Rhabdomyosarcoma Therapy In Vitro: A Systematic Review

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, constitutes approximately 40% of all recorded soft tissue tumors and is associated with a poor prognosis, with survival rates of less than 20% at 3 years. The development of resistance to cytotoxic drugs is a primary contributor to therapeutic failure. Consequently, the exploration of new therapeutic strategies is of vital importance. The potential use of plant extracts and their bioactive compounds emerges as a complementary treatment for this type of cancer. This systematic review focuses on research related to plant extracts or isolated bioactive compounds exhibiting antitumor activity against RMS cells. Literature searches were conducted in PubMed, Scopus, Cochrane, and WOS. A total of 173 articles published to date were identified, although only 40 were finally included to meet the inclusion criteria. Furthermore, many of these compounds are readily available and have reduced cytotoxicity, showing an apoptosis-mediated mechanism of action to induce tumor cell death. Interestingly, their use combined with chemotherapy or loaded with nanoparticles achieves better results by reducing toxicity and/or facilitating entry into tumor cells. Future in vivo studies will be necessary to verify the utility of these natural compounds as a therapeutic tool for RMS.Spanish Ministry of Science and Innovation (FEDER) (CPP2022-009967 and CPP2022-010017)Spanish Ministry of Universities and Science (RTC2019-006870-1

Differential chemotherapeutic regimen cytotoxicity against pancreatic cancer stem cells: a preliminary in vitro study

We are grateful to Scientific Instrumentation Center (CIC) from the Granada University.Introducción: El tratamiento del cáncer de páncreas en estadios avanzados se basa en diferentes regímenes de quimioterapia. Las células madre cancerosas son responsables de la quimiorresistencia tumoral y la recurrencia tras tratamientos en etapa adyuvante y metastásica. El objetivo de este artículo fue evaluar cómo estos regímenes quimioterapéuticos afectan a la proporción de células madre cancerosas y la expresión de sus marcadores. Método: Utilizamos la línea celular de adenocarcinoma pancreático PANC-1 como modelo para aplicar diferentes protocolos quimioterapéuticos (monoterapia y terapia combinada) utilizando 5-Fluorouracilo, Oxaliplatino, Irino tecán, Gemcitabina y Abraxane. Resultados: Tras analizar mediante RT-qPCR diferentes marcadores de células madre tumorales (SOX2, OCT4, CD133, CD44 y CD24) en células de cáncer de páncreas tratadas con diferentes protocolos quimioterapéuticos, el Oxaliplatino y la Gemcitabina en monoterapia fueron los quimioterápicos que seleccionaron en mayor medida las células madre cancerosas mientras que el protocolo FOLFIRI las disminuyó. Conclusiones: En cuanto a la selección de marcadores, ha sido mucho mayor en el caso de Gemcitabina en monoterapia. En conclusión, estos hallazgos podrían mejorar y personalizar la terapia del cáncer de páncreas.Introduction: Pancreatic cancer treatment in advanced stages is based on different chemotherapy regimens. Can cer stem cells are responsible for tumor chemoresistance and recurrence in adjuvant and metastatic settings. The objective of this article was to evaluate how these chemotherapeutic regimens affect the proportion of cancer stem cells and the expression of stemness markers. Method: We used the pancreatic adenocarcinoma cell line PANC-1 as a model to apply different chemotherapeu tic protocols (monotherapy and combined therapy) using 5-Fluorouracil, Oxaliplatin, Irinotecan, Gemcitabine and Abraxane. Results: After analyzing different tumor stem cell markers (SOX2, OCT4, CD133, CD44 and CD24) in pancreatic can cer cells treated with different chemotherapeutic protocols by means of RT-qPCR, Oxaliplatin and Gemcitabine in monotherapy were the chemotherapies that selected the most cancer stem cells while the FOLFIRI protocol de creased them. Conclusions: Regarding the selection of markers, it has been much higher in the case of Gemcitabine alone. In conclusion, these findings could improve and personalize pancreatic cancer therapy.This work was supported by funds from group CTS-107 (Andalusian Government). F. J. Q. acknowledges the FPU2019 grant from the Ministerio de Educacion Ciencia y Deporte y Competitividad (Spain)

Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review

Sarcomas are a diverse group of neoplasms with an incidence rate of 15% of childhood cancers. They exhibit a high tendency to develop early metastases and are often resistant to available treatments, resulting in poor prognosis and survival. In this context, cancer stem cells (CSCs) have been implicated in recurrence, metastasis, and drug resistance, making the search for diagnostic and prognostic biomarkers of the disease crucial. The objective of this systematic review was to analyze the expression of CSC biomarkers both after isolation from in vitro cell lines and from the complete cell population of patient tumor samples. A total of 228 publications from January 2011 to June 2021 was retrieved from different databases, of which 35 articles were included for analysis. The studies demonstrated significant heterogeneity in both the markers detected and the CSC isolation techniques used. ALDH was identified as a common marker in various types of sarcomas. In conclusion, the identification of CSC markers in sarcomas may facilitate the development of personalized medicine and improve treatment outcomes.CTS-107 (Andalusian Government

Experimental Tumor Induction and Evaluation of Its Treatment in the Chicken Embryo Chorioallantoic Membrane Model: A Systematic Review

The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.Instituto de Salud Carlos III (PI19/ 01478-FEDER)Project PMPTA22/00136 funded by the Instituto de Salud Carlos III-FEDERCPP2022-009967 and CPP2022-010017 Project from the Spanish Ministry of Science and Innovation (FEDER

Nuevos escenarios para la innovación educativa : el Grupo CREA (Centros en Red para las Enseñanza Activas) y la renovación metodológica de los centros educativos

Convocatoria Proyectos de innovación de Extremadura 2018/2019Proyecto que agrupa a cinco centros educativos: el IES Jaranda (Jarandilla de la Vera, Cáceres), el IESO Sierra la Mesta (Santa Amalia, Badajoz), el IES Albarrega (Mérida, Badajoz), el IESO Val de Xálima (Valverde del Fresno, Badajoz), IESO Matías Ramón Martínez (Burguillos del Cerro, Badajoz) que conforman el Grupo CREA y que comparten una trayectoria común: el uso de metodologías educativas activas. A las iniciativas innovadoras llevadas a cabo colectivamente se suman las individuales de cada centro debido a la particularidad de cada uno de ellos. Los objetivos principales del proyecto son: la creación de una estructura organizativa y de coordinación entre los distintos centros participantes que permita la planificación y puesta en marcha de acciones educativas conjuntas; la introducción de cambios organizativos, funcionales, espaciales y metodológicos para llevar a cabo aprendizajes basados en proyectos, orientados al servicio a la comunidad y a los problemas sociales, centrados en el aprendizaje cooperativo, etc.; el diseño y desarrollo de programas de innovación coordinados entre los distintos centros educativos participantes; el establecimiento de mecanismos de coordinación para hacer efectiva la comunicación, el intercambio de información, el análisis y la reflexión del profesorado participante en los programas de innovación de cada uno de los centros; la formación conjunta del profesorado; el desarrollo de proyectos conjuntos para los alumnos participantes, su conexión en entornos virtuales, el intercambio de experiencias en encuentros periódicos, etc. y la generación y fomento de una nueva red creando un portal web y un espacio de comunicación e intercambio de documentaciónExtremaduraES