The dark side of radiotherapy-induced cell death in cancer

The work of Dr. Sainz is supported by a Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain, a Coordinated grant from the Fundación Asociación Española Contra el Cáncer (AECC), and a Fondo de Investigaciones Sanitarias (FIS) grant PI15/ 01507 (co-financed through Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”) from the Instituto de Salud Carlos III (ISCIII), Spai

Diferencias de género en pacientes con obesidad mórbida tributarios de cirugía bariátrica

The aim of this study was to assess the differences by gender of patients with morbid obesity that are bariatric surgery candidates. The sample was composed of 441 patients evaluated through a clinical interview, the International Personality Disorder Examination (IPDE, version CIE-10) and the Gardner´s Body Image Assessment Scale. The results show that obese women sought treatment twice as much as men. Moreover, we found other gender differences, such as more Axis I pathology in the female group, and women showing a higher level of dissatisfaction and a more distorted body image than men.El objetivo de este estudio fue valorar las diferencias por género de los pacientes con obesidad mórbida, candidatos a cirugía bariátrica. La muestra se compone de 441 pacientes evaluados mediante entrevista clínica, el Examen Internacional de los Trastornos de Personalidad (IPDE, versión CIE-10) y la Escala de Evaluación de la Imagen Corporal de Gardner. Los resultados muestran que las mujeres con obesidad solicitan este tipo de tratamiento dos veces más que los hombres. Además, se hallaron otras diferencias de género, tales como mayor patología del Eje I, mayor índice de insatisfacción, y mayor de distorsión de la imagen corporal en el grupo de mujeres.

Utilización de instrumentos de clasificación de pacientes: análisis de la producción del conocimiento brasileño

Objective To analyze the production of scientific knowledge about the use of patients’ classification instruments in care and management practice in Brazil. Method Integrative literature review with databases search in: Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System on-line (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and SCOPUS, between January 2002 through December 2013. Results 1,194 studies were found, 31 met the inclusion criteria. We observed a higher number of studies in the category care plans and workload (n=15), followed by the category evaluation of psychometric properties (n=14). Conclusion Brazilian knowledge production has not yet investigated some purposes of using instruments for classifying patients in professional nursing practice. The identification of unexplored areas can guide future research on the topic.
Objetivo Analizar la producción del conocimiento científico acerca de la utilización de instrumentos de clasificación de pacientes en la práctica asistencial y de gestión en Brasil. Método Revisión integradora de la literatura con consulta a las bases de datos: Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Medical Literature Analysis and Retrieval System on-line (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL) y SCOPUS, relativas al período de enero de 2002 a diciembre de 2013. Resultados De las 1.194 publicaciones encontradas, 31 atendieron a los criterios de selección. Se observó una mayor cantidad de artículos en la categoría perfil asistencial y carga laboral (n=15), seguidos de la categoría evaluación de las propiedades psicométricas (n=14). Conclusión La producción nacional todavía no ha investigado algunas finalidades de utilización de instrumentos de clasificación de pacientes en la práctica profesional del enfermero. La identificación de áreas aún no exploradas podrá orientar futuras investigaciones acerca de la temática.Objective To analyze the production of scientific knowledge about the use of patients’ classification instruments in care and management practice in Brazil. Method Integrative literature review with databases search in: Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System on-line (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and SCOPUS, between January 2002 through December 2013. Results 1,194 studies were found, 31 met the inclusion criteria. We observed a higher number of studies in the category care plans and workload (n=15), followed by the category evaluation of psychometric properties (n=14). Conclusion Brazilian knowledge production has not yet investigated some purposes of using instruments for classifying patients in professional nursing practice. The identification of unexplored areas can guide future research on the topic.


Fatty Acid Synthase Inhibitor G28 Shows Anticancer Activity in EGFR Tyrosine Kinase Inhibitor Resistant Lung Adenocarcinoma Models

Epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs) are effectivetherapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor an EGFR activatingmutation. However, this treatment is not curative due to primary and secondary resistance suchas T790M mutation in exon 20. Recently, activation of transducer and activator of transcription 3(STAT3) in NSCLC appeared as an alternative resistance mechanism allowing cancer cells to elude theEGFR signaling. Overexpression of fatty acid synthase (FASN), a multifunctional enzyme essentialfor endogenous lipogenesis, has been related to resistance and the regulation of the EGFR/Jak2/STATsignaling pathways. Using EGFR mutated (EGFRm) NSCLC sensitive and EGFR TKIs' resistantmodels (Gefitinib Resistant, GR) we studied the role of the natural polyphenolic anti-FASN compound(−)-epigallocatechin-3-gallate (EGCG), and its derivative G28 to overcome EGFR TKIs' resistance.We show that G28's cytotoxicity is independent of TKIs' resistance mechanisms displaying synergisticeffects in combination with gefitinib and osimertinib in the resistant T790M negative (T790M−)model and showing a reduction of activated EGFR and STAT3 in T790M positive (T790M+) models.Our results provide the bases for further investigation of G28 in combination with TKIs to overcomethe EGFR TKI resistance in NSCLC

Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells

Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC

¿Es posible una (verdadera) competencia clave relacionada con lo motriz?. La competencia corporal

La Educación Física continúa luchando por el reconocimiento social desde hace años. En la actualidad, además del aumento de horas, pretende la incorporación de una competencia motriz a las competencias que desde Europa se consideran clave. El objetivo de este artículo es reflexionar acerca de una competencia vinculada a los aspectos motrices, psicomotrices o corporales desde la perspectiva transversal que poseen las competencias clave y no desde el tradicional enfoque propio y exclusivo de nuestra materia. Se analizan los fundamentos de las competencias para ser consideradas clave y la aplicación coherente de las mismas para contribuir al desarrollo verdaderamente integral del alumnado. En este sentido, lo corporal lo consideramos clave, aunque no desde un enfoque motriz propio y exclusivo del área de Educación Física. Por ello, presentamos una serie de justificaciones y argumentaciones para proporcionar, a lo que hemos denominado Competencia Corporal Clave, una serie de dimensiones que pueden ser verdaderamente trabajadas desde todas las materias, contribuyendo así a la misma, al desarrollo integral y a su transferencia a la vida activa y adulta

Increased levels of rictor prevent mutant huntingtin-induced neuronal degeneration

Rictor associates with mTOR to form the mTORC2 complex, which activity regulates neuronal function and survival. Neurodegenerative diseases are characterized by the presence of neuronal dysfunction and cell death in specific brain regions such as for example Huntington's disease (HD), which is characterized by the loss of striatal projection neurons leading to motor dysfunction. Although HD is caused by the expression of mutant huntingtin, cell death occurs gradually suggesting that neurons have the capability to activate compensatory mechanisms to deal with neuronal dysfunction and later cell death. Here, we analyzed whether mTORC2 activity could be altered by the presence of mutant huntingtin. We observed that Rictor levels are specifically increased in the striatum of HD mouse models and in the putamen of HD patients. Rictor-mTOR interaction and the phosphorylation levels of Akt, one of the targets of the mTORC2 complex, were increased in the striatum of the R6/1 mouse model of HD suggesting increased mTORC2 signaling. Interestingly, acute downregulation of Rictor in striatal cells in vitro reduced mTORC2 activity, as shown by reduced levels of phospho-Akt, and increased mutant huntingtin-induced cell death. Accordingly, overexpression of Rictor increased mTORC2 activity counteracting cell death. Furthermore, normalization of endogenous Rictor levels in the striatum of R6/1 mouse worsened motor symptoms suggesting an induction of neuronal dysfunction. In conclusion, our results suggest that increased Rictor striatal levels could counteract neuronal dysfunction induced by mutant huntingtin

Inhibition of mitochondrial dynamics preferentially targets pancreatic cancer cells with enhanced tumorigenic and invasive potential

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors, partly due to its intrinsic aggressiveness, metastatic potential, and chemoresistance of the contained cancer stem cells (CSCs). Pancreatic CSCs strongly rely on mitochondrial metabolism to maintain their stemness, therefore representing a putative target for their elimination. Since mitochondrial homeostasis de-pends on the tightly controlled balance between fusion and fission processes, namely mitochondrial dynamics, we aim to study this mechanism in the context of stemness. In human PDAC tissues, the mitochondrial fission gene DNM1L (DRP1) was overexpressed and positively correlated with the stemness signature. Moreover, we observe that primary human CSCs display smaller mitochondria and a higher DRP1/MFN2 expression ratio, indicating the activation of the mitochondrial fission. In-terestingly, treatment with the DRP1 inhibitor mDivi-1 induced dose-dependent apoptosis, especially in CD133+ CSCs, due to the accumulation of dysfunctional mitochondria and the subsequent energy crisis in this subpopulation. Mechanistically, mDivi-1 inhibited stemness-related features, such as self-renewal, tumorigenicity, and invasiveness and chemosensitized the cells to the cytotoxic effects of Gemcitabine. In summary, mitochondrial fission is an essential process for pancreatic CSCs and represents an attractive target for designing novel multimodal treatments that will more efficiently eliminate cells with high tumorigenic potentialThis research was funded by the Pancreatic Cancer Research Fund, 2015 Award Round (P.S., C.H.); the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n 602783 (CAM-PaC) (C.H.), theWorldwide Cancer Research Charity together with Fundación Científica Asociación Española contra el Cáncer (FCAECC) (19-0250) (P.S.); A Fero Foundation grant and a Coordinated grant (GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC) (B.S.J.); and the Instituto de Salud Carlos III through the Miguel Servet Program (CP16/00121) and Fondo de Investigaciones Sanitarias (PI17/00082) (both co-financed by European funds (FSE: “El FSE invierte en tu futuro” and FEDER: “Una manera de hacer Europa,” respectively) (P.S.