SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.

Immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies, in a patient with melanoma treated with BRAF/MEK inhibitors.

The effect of serine/threonine-protein kinase B-Raf/mitogen-activated protein kinase (BRAF/MEK) inhibitors on the immune system is not clearly described, but rare cases of autoimmune phenomena have been reported. The clinical case we present below is the first report of a necrotizing myopathy related to dabrafenib/trametinib treatment. A 48-year-old man started dabrafenib/trametinib for stage IV BRAF-V600E mutated cutaneous melanoma. After the first month, he presented with grade 3 pyrexia (Common Terminology Criteria for Adverse Events [CTCAE] v.5.0.) and increased creatinine-kinase levels. A diagnosis of immune-mediated necrotizing myopathy, antisignal recognition particle (anit-SRP) positive, was made. At disease progression, dabrafenib/trametinib was restarted, triggering a new episode of grade 2 pyrexia and myositis. Treatment was changed to encorafenib/binimetinib without repeating pyrexia or limiting creatinine-kinase elevation, presenting even a loss of anti-SRP antibodies. Given the temporal relationship, the fact that re-exposition induced a new worsening of the myopathy and the loss of the anti-SRP antibodies after changing treatment, we infer that there possibly is a clear relationship between dabrafenib/trametinib treatment and the myopathy.

Fluid consumption in lithium-treated rats: roles of stimulus novelty and context novelty.

In 5 experiments thirsty rats received an injection of lithium chloride or of saline, and their consumption of fluid was monitored at 5-min intervals for 30 min. The novelty of the fluid and the novelty of the test context was varied. In Experiment 1 a novel fluid (a sucrose solution) was offered in a novel context; in Experiment 2 the fluid was novel and the context was familiar (the home cage); in Experiment 3 the fluid was familiar and the context was novel; and in Experiment 4 both fluid and context were familiar. Lithium influenced fluid consumption in those designs that included at least one novel feature (Experiments 1, 2, and 3, but not in Experiment 4). Consumption was initially enhanced (with respect to the controls) when the context was novel, but was suppressed when the fluid was novel. In Experiment 5, the flavor was over-ingested after lithium treatment when it was presented in a short (5 min) test conducted in a novel place, but was rejected in a subsequent consumption in the home cages. It is argued that the effect of lithium depends on two factors: enhanced attention to salient cues that modifies the exploratory responses evoked by a novel context; rapid conditioning of an aversion when the fluid consumed is novel. Implications for the use of fluid consumption as an index of lithium-induced nausea are considered.

Descripción del patrón de consumo de golosinas en escolares de 5º curso de Educación Primaria de la Ciudad Autónoma de Ceuta / No disponible

Fundamentos: El consumo de golosinas es habitual enjóvenes y adolescentes, particularmente incidente en elprimer periodo de la adolescencia. Está asociado a lapatogenia de enfermedades como la caries y la obesidad.El objetivo general del estudio consiste en establecer elpatrón de consumo de golosinas de los escolares de 5ºde Primaria en la Ciudad Autónoma de Ceuta.Material y método: Se realizó un estudio transversal descriptivosobre una muestra representativa de 293 sujetos,mediante un cuestionario diseñado ad hoc. Los resultadosse analizan agrupados en nueve dimensiones:frecuencia y cantidad, momento de consumo, modo deingesta, lugar de compra y de consumo, existencia deconsumo compartido, criterios de elección, gasto diario,conocimiento del daño que puede provocar y existenciade limitación ajena o propia.Conclusiones: Este consumo es habitual y repartido en elhorario de tarde, por lo que aumenta su poder cariogénico.Se realiza en solitario en una tercera parte de los sujetos,reflejando un cierto grado de compulsión en el hábito deconsumo. Tienen conocimiento sobre la insalubridad delconsumo de golosinas pero, contradictoriamente, sonconsumidores habituales y, además, lo autoevalúan comonormal. No existe un excesivo control familiar, reflejandoun cierto conformismo con este consumo(AU)

Background: The consumption of candy is habitual foryoung people and teenagers, particularly during the firstperiod of teenage. It is associated with the pathogeny ofdiseases such as caries and obesity. The general objectiveof this research is to establish the candy consumptionpattern of 5th grade students from the Autonomous Cityof Ceuta.Methods: A transversal, descriptive study has beenrealized, with a representative sample of 293 subjects,using an ad-hoc questionnaire. Results are analysedgrouped in nine dimensions: frequency and quantity,moment of consumption, type of intake, place of purchaseand consumption, existence of shared consumption,criteria of election, daily expense, knowledge about theharm it may cause and existence of external or personalconstraints.Conclusions: Consumption is frequent and spread alongthe afternoon, enhancing its cariogenic power.Furthermore, candies are taken on their own by one thirdof the subjects, reflecting a certain degree of compulsionin the habit of candy consumption. Consumers know aboutthe unhealthiness of candy consumption but,contradictorily, they are habitual consumers and, besides,they consider it as normal. There is not an excessive familycontrol, showing a certain conformism about thisconsumption(AU)