Caregiving role and Psychosocial and individual factors: a systematic review

Emotional intelligence (EI) refers to the ability to perceive, express, understand, and manage emotions. Current research indicates that it may protect against the emotional burden experienced in certain professions. This article aims to provide an updated systematic review of existing instruments to assess EI in professionals, focusing on the description of their characteristics as well as their psychometric properties (reliability and validity). A literature search was conducted in Web of Science (WoS). A total of 2761 items met the eligibility criteria, from which a total of 40 different instruments were extracted and analysed. Most were based on three main models (i.e., skill-based, trait-based, and mixed), which differ in the way they conceptualize and measure EI. All have been shown to have advantages and disadvantages inherent to the type of tool. The instruments reported in the largest number of studies are Emotional Quotient Inventory (EQ-i), Schutte Self Report-Inventory (SSRI), Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT 2.0), Trait Meta-Mood Scale (TMMS), Wong and Law's Emotional Intelligence Scale (WLEIS), and Trait Emotional Intelligence Questionnaire (TEIQue). The main measure of the estimated reliability has been internal consistency, and the construction of EI measures was predominantly based on linear modelling or classical test theory. The study has limitations: we only searched a single database, the impossibility of estimating inter-rater reliability, and non-compliance with some items required by PRISMA

AKT and JUN are differentially activated in mesenchymal stem cells after infection with human and canine oncolytic adenoviruses

Factor de impacto: 5,987 Q1There is increasing evidence about the use of oncolytic adenoviruses (Ads) as promising immunotherapy agents. We have previously demonstrated the clinical efficiency of mesenchymal stem cells (MSCs) infected with oncolytic Ads as an antitumoral immunotherapy (called Celyvir) in human and canine patients, using ICOVIR-5 or ICOCAV17 as human and canine oncolytic Ads, respectively. Considering the better clinical outcomes of canine patients, in this study we searched for differences in cellular responses of human and canine MSCs to Ad infection that may help understand the mechanisms leading to higher antitumor immune response. We found that infection of human and canine MSCs with ICOVIR-5 or ICOCAV17 did not activate the NF-κB pathway or the interferon regulatory factors IRF3 and IRF7. However, we observed differences in the profile of cytokines secretion, as infection of canine MSCs with ICOCAV17 resulted in lower secretion of several cytokines. Moreover, we showed that infection of human MSCs with ICOVIR-5 increased the phosphorylation of a number of proteins, including AKT and c-JUN. Finally, we demonstrated that differences in regulation of AKT and c-JUN in human and canine MSCs by ICOVIR-5 or ICOCAV17 are intrinsic to each virus. Our findings suggest that ICOCAV17 induces a more limited host response in canine MSCs, which may be related to a better clinical outcome. This result opens the possibility to develop new human oncolytic Ads with these specific properties. In addition, this improvement could be imitated by selecting specific human MSC on the basis of a limited host response after Ad infection.This study was funded by Instituto de Salud Carlos III (PI14CIII/00005 and PI17CIII/00013 grants), Consejería de Educación, Juventud y Deporte of Comunidad de Madrid (P2017/BMD-3692 grant), Fundación Oncohematología Infantil, AFANION, and Asociación Pablo Ugarte, whose support we gratefully acknowledge.S

Toll-like Receptor Signaling-deficient Cells Enhance Antitumor Activity of Cell-based Immunotherapy by Increasing Tumor Homing

Cancer immunotherapy aims to activate the immune system. Some immunotherapeutic agents can be loaded in carrier cells for delivering to the tumors. However, a challenge with cell-based therapies is the selection of the appropriate cells to produce effective clinical outcomes. We hypothesize that therapies based on cells presenting a natural low proinflammatory profile ("silent cells") in the peripheral blood would result in better antitumor responses by increasing their homing to the tumor site. We studied our hypothesis in an immunotherapy model consisting of mesenchymal stromal cells (MSCs) carrying oncolytic adenoviruses for the treatment of immunocompetent mice. Toll-like receptor signaling-deficient cells (TLR4, TLR9, or MyD88 knockout) were used as "silent cells," while regular MSCs were used as control. Although in vitro migration was similar in regular and knockout carrier cells, in vivo tumor homing of silent cells was significantly higher after systemic administration. This better homing to the tumor site was highly related to the mild immune response triggered by these silent cells in peripheral blood. As a result, the use of silent cells significantly improved the antitumor efficacy of the treatment in comparison with the use of regular MSCs. While cancer immunotherapies generally aim to boost local immune responses in the tumor microenvironment, low systemic inflammation after systemic administration of the treatment may indeed enhance their tumor homing and improve the overall antitumor effect. These findings highlight the importance of selecting appropriate donor cells as therapeutic carriers in cell-based therapies for cancer treatment. Cells carrying drugs, virus, or other antitumor agents are commonly used for the treatment of cancer. This research shows that silent cells are excellent carriers for immunotherapies, improving tumor homing and enhancing the antitumor effect.This study was funded by Instituto de Salud Carlos III (grants PI14CIII/00005, PI17CIII/00013, and ISCIII-PFIS FI18CIII/00017), Consejería de Educación, Juventud y Deporte of Comunidad de Madrid (grant P2017/BMD-3692), Fundación Oncohematología Infantil, Asociación Pablo Ugarte and AFANION, whose support we gratefully acknowledge.S

Ocoxin Modulates Cancer Stem Cells and M2 Macrophage Polarization in Glioblastoma

Glioblastoma (GBM) is the most common and devastating primary brain tumor. The presence of cancer stem cells (CSCs) has been linked to their therapy resistance. Molecular and cellular components of the tumor microenvironment also play a fundamental role in the aggressiveness of these tumors. In particular, high levels of hypoxia and reactive oxygen species participate in several aspects of GBM biology. Moreover, GBM contains a large number of macrophages, which normally behave as immunosuppressive tumor-supportive cells. In fact, the presence of both, hypoxia and M2-like macrophages, correlates with malignancy and poor prognosis in gliomas. Antioxidant agents, as nutritional supplements, might have antitumor activity. Ocoxin® oral solution (OOS), in particular, has anti-inflammatory and antioxidant properties, as well as antitumor properties in several neoplasia, without known side effects. Here, we describe how OOS affects stem cell properties in certain GBMs, slowing down their tumor growth. In parallel, OOS has a direct effect on macrophage polarization in vitro and in vivo, inhibiting the protumoral features of M2 macrophages. Therefore, OOS could be a feasible candidate to be used in combination therapies during GBM treatment because it can target the highly resilient CSCs as well as their supportive immune microenvironment, without adding toxicity to conventional treatments.The authors would like to acknowledge Atanasio Pandiella for critical comments on the manuscript, Rosella Galli for donating GBM1, and Jacqueline Gutiérrez, Daniela Moiseev, Daniel Batzan, and Mario Alia for their technical support. RG has been funded by the Fundación Científica Asociación Española Contra el Cáncer. Research has been funded by grants from Fundación Científica Asociación Española Contra el Cáncer (18/006) to JMS; from MINECO: Acción Estratégica en Salud (AES) PI13/01258 to AHL; AES PI17/01621 to JMS; Red Temática de Investigación Cooperativa en Cancer (RTICC) RD12/0036/0027 to AHL, JMS, APN, and PSG; and MINECO-RETOS/FEDER SAF2015-65175 to PSG.S

Tumor-derived pericytes driven by egfr mutations govern the vascular and immune microenvironment of gliomas

The extraordinary plasticity of glioma cells allows them to contribute to different cellular compartments in tumor vessels, reinforcing the vascular architecture. It was recently revealed that targeting glioma-derived pericytes, which represent a big percentage of the mural cell population in aggressive tumors, increases the permeability of the vessels and improves the efficiency of chemotherapy. However, the molecular determinants of this transdifferentiation process have not been elucidated. Here we show that mutations in EGFR stimulate the capacity of glioma cells to function as pericytes in a BMX- (bone marrow and X-linked) and SOX9-dependent manner. Subsequent activation of platelet-derived growth factor receptor beta in the vessel walls of EGFR-mutant gliomas stabilized the vasculature and facilitated the recruitment of immune cells. These changes in the tumor microenvironment conferred a growth advantage to the tumors but also rendered them sensitive to pericyte-targeting molecules such as ibrutinib or sunitinib. In the absence of EGFR mutations, high-grade gliomas were enriched in blood vessels, but showed a highly disrupted blood–brain barrier due to the decreased BMX/SOX9 activation and pericyte coverage, which led to poor oxygenation, necrosis, and hypoxia. Overall, these findings identify EGFR mutations as key regulators of the glioma-to-pericyte transdifferentiation, highlighting the intricate relationship between the tumor cells and their vascular and immune milieu. Our results lay the foundations for a vascular-dependent stratification of gliomas and suggest different therapeutic vulnerabilities determined by the genetic status of EGFR.This work was supported by FONDECYT grant (1140697 to V. Palma), CONICYT Fellowship (to B.S. Casas), by Ministerio de Economía y Competitividad and FEDER funds (PI13/01258 to A. Hernandez-Laín; PI17/01621 to J.M. Sepulveda-S anchez; and PI16/01580 and DTS18/00181 to A. Matheu), by Young Employment Initiative (Comunidad de Madrid) to M. Garranzo-Asensio, by “Asociacion Espanola contra ~ el Cancer” (AECC) grants (INVES192GARG to R. Gargini; GCTRA16015SEDA to J.M. Sepulveda-S anchez); and by Ministerio de Ciencia, Innovacion y Universidades and FEDER funds (RTI2018-093596 to P. Sanchez-Gomez).Peer reviewe

MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma

Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferation, induced apoptosis, reduced invasion, migration and regulated EMT by an increase of E-cadherin and a decrease of ß-catenin and vimentin. The silencing of EZH2 mimicked the impact of miR-33b overexpression. Furthermore, the inhibition of miR-33b induces cell proliferation, invasion, migration, EMT, and EZH2 expression in non-tumorigenic cells. Importantly, the Kaplan-Meier analysis showed a significant association between high miR-33b expression and better overall survival. These results suggest miR-33b as a suppressive miRNA that could inhibit tumor metastasis and invasion in HER2+ BC partly by impeding EMT through the repression of the MYC-EZH2 loop

Papel de ephrina B1 y ephrina B2 en el desarrollo y la función del timo

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 27/06/2011.Fac. de Ciencias BiológicasTRUEProQuestpu

Papel de ephrina B1 y ephrina B2 en el desarrollo y la función del timo

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 27/06/2011.Fac. de Ciencias BiológicasTRUEProQuestpu

Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice.

Oncolytic virotherapy uses oncolytic viruses that selectively replicate in cancer cells. The use of cellular vehicles with migration ability to tumors has been considered to increase their delivery to target sites. Following this approach, the antitumor efficacy of the treatment Celyvir (mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5) has been demonstrated in patients with neuroblastoma. However, the better efficacy of syngeneic or allogeneic mesenchymal stem cells as cell carriers and the specific role of the immune system in this therapy are still unknown. In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir-treated groups. While non-treated tumors presented higher density of infiltrating immune cells in the periphery of the tumor, both syngeneic and allogeneic Celyvir-treated groups presented higher infiltration of CD45+ cells in the core of the tumor. Therefore, these results suggest that syngeneic and allogeneic Celyvir induce systemic activation of the immune system, similar antitumor effect and a higher intratumoral infiltration of leukocytes.Funding for this research was provided by: Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (P2010/BMD-2420) Asociación Pablo Ugarte Fondo de Investigaciones Sanitarias (PI17/00013, PI14CIII/00005) Fundación Oncohematología Infantil AFANIONS

Producto de combinación que comprende una célula madre mesenquimatosa modificada y una sustancia antigénica.

La presente solicitud proporciona un producto de combinación para el tratamiento de cáncer. El producto de combinación comprende (i) una célula madre mesenquimatosa modificada, y (ii) una sustancia antigénica. Además, la presente solicitud también proporciona un método para la producción de una célula madre mesenquimatosa modificada que comprende un parásito intracelular y un kit que comprende (a) una célula madre mesenquimatosa, (b) una sustancia antigénica y (c) un inhibidor del receptor de tipo Toll 4 y/o del receptor de tipo Toll 9.REIVINDICACIONES 1. Producto de combinación que comprende: (i) una célula madre mesenquimatosa modificada en la que el receptor de tipo Toll 4 y/o el receptor de tipo Toll 9 están inhibidos; y (ii) una sustancia antigénica. 2. Producto de combinación según la reivindicación 1, en el que el receptor de tipo Toll 4 está inhibido. 3. Producto de combinación según la reivindicación 1, en el que el receptor de tipo Toll 9 está inhibido. 4. Producto de combinación según una cualquiera de las reivindicaciones 1-3, en el que la sustancia antigénica es un parásito intracelular. 5. Producto de combinación según la reivindicación 4, en el que el parásito intracelular es un virus oncolítico, preferiblemente el virus oncolítico se selecciona del grupo que consiste en adenovirus, reovirus, virus del sarampión, virus del herpes simple, virus de la enfermedad de Newcastle, virus vaccinia, virus de Coxsackie y virus del valle del Séneca. 6. Producto de combinación según la reivindicación 5, en el que el virus oncolítico es ICOVIR-5. 7. Producto de combinación según cualquiera de las reivindicaciones anteriores, en el que la célula madre mesenquimatosa deriva de médula ósea, placenta, cordón umbilical, membrana amniótica, sangre menstrual, sangre periférica, glándula salivar, piel y prepucio, líquido sinovial, líquido amniótico, endometrio, tejido adiposo, sangre del cordón umbilical y/o tejido dental. 8. Producto de combinación según una cualquiera de las reivindicaciones anteriores, en el que el producto de combinación es una composición. 9. Composición farmacéutica que comprende la composición según la reivindicación 8, y un portador o diluyente farmacéuticamente aceptable, y/o un adyuvante farmacéuticamente aceptable. 10. Composición farmacéutica según la reivindicación 9, en la que la composición farmacéutica comprende además un agente quimioterápico. 11. Producto de combinación según las reivindicaciones 1-8 o composición farmacéutica según las reivindicaciones 9 ó 10 para su uso como medicamento. 12. Producto de combinación según las reivindicaciones 1-8 o composición farmacéutica según las reivindicaciones 9 ó 10 para su uso en el tratamiento de un tumor sólido. 13. Producto de combinación o composición farmacéutica para su uso según la reivindicación 12, en los que el tumor sólido es un cáncer de cerebro, cáncer de pulmón, cáncer de riñón, cáncer de ovarios y/o cáncer de hígado. 14. Producto de combinación o composición farmacéutica para su uso según una cualquiera de las reivindicaciones 12-13, en los que el tratamiento se usa en combinación con quimioterapia y/o radioterapia. 15. Método para la producción de células madre mesenquimatosas modificadas que comprenden un parásito intracelular, que comprende las etapas de: (1) aislar células madre mesenquimatosas a partir de una muestra aislada; (2) cultivar las células madre mesenquimatosas; (3) inhibir el receptor de tipo Toll 4 y/o el receptor de tipo Toll 9 de las células madre mesenquimatosas aisladas; y (4) infectar las células madre mesenquimatosas con un parásito intracelular. 16. Método según la reivindicación 15, que comprende además una etapa de irradiación con rayos X entre las etapas (3) y (4). 17. Kit que comprende: (a) una célula madre mesenquimatosa; (b) una sustancia antigénica; y (c) un inhibidor del receptor de tipo Toll 4 y/o del receptor de tipo Toll 9 seleccionado del grupo que consiste en: (i) ARN de interferencia pequeño; (ii) vectores para terapia génica, preferiblemente vectores para terapia génica que comprenden el sistema CRISPR/Cas9; (iii) un inhibidor de molécula pequeña bioactivo del receptor de tipo Toll 4 seleccionado del grupo que consiste en 3,4,6-triacetato de isopropil-2-(acetilamino)-2-desoxi-a-D-glucopiranósido, resatorvid, eritorán y un péptido con la secuencia KYSFKLILAEYRRRRRRRRR (SEQ ID NO: 1), y/o un inhibidor de molécula pequeña bioactivo del receptor de tipo Toll 9 seleccionado del grupo que consiste en un nucleótido que comprende la secuencia TTAGGG, ODN 2088, ODN 4084-F, ODN INH-1, ODN-INH-18, ODN A151, G-ODN, 3-[4-(6-(3-(dimetilamino)propoxi)benzo[d]oxazol-2-il)fenoxi]-N,N-dimetilpropan-1-amina, 6-[3-(pirrolidin-1-il)propoxi)-2-(4-(3-(pirrolidin-1-il)propoxi)fenil]benzo[d]oxazol; y (iv) un anticuerpo neutralizante que se une a la región extracelular del receptor de tipo Toll 4 y/o el receptor de tipo Toll 9. 18. Kit según la reivindicación 17, en el que la sustancia antigénica es un parásito intracelular.Cuando una patente se hace internacional, se puede encontrar en el idioma de cada país en que se ha solicitado. En Espacenet se tiene acceso a los documentos en cada idioma.Instituto de Salud Carlos IIISolicitud de patent