Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy

The PI3K pathway is hyperactivated in most cancers, yet the capacity of PI3K inhibitors to induce tumor cell death is limited. The efficacy of PI3K inhibition can also derive from interference with the cancer cells’ ability to respond to stromal signals, as illustrated by the approved PI3Kδ inhibitor Idelalisib in B-cell malignancies. Inhibition of the leukocyte-enriched PI3Kδ or PI3Kγ may unleash more potent anti-tumor T-cell responses, by inhibiting regulatory T-cells and immune-suppressive myeloid cells. Moreover, tumor angiogenesis may be targeted by PI3K inhibitors to enhance cancer therapy. Future work should therefore focus on the effects of PI3K inhibitors on the stroma, in addition to their direct effects on tumors. SIGNIFICANCE: The PI3K pathway extends beyond the direct regulation of cancer cell proliferation and survival. In B-cell malignancies, targeting PI3K purges the tumor cells from their protective microenvironment. Moreover, we propose that PI3K isoform-selective inhibitors may be exploited in the context of cancer immunotherapy and by targeting angiogenesis to improve drug and immune cell deliver

Aplicabilidad del test MABC en escolares con síndrome de down

El presente estudio analiza la aplicabilidad de tests de coordinación y habilidad motriz, diseñados para la población infantil general, en escolares de Educación Física Especial. Para el estudio se selecciona una muestra de niños y niñas con síndrome de Down, de 9 y 10 años, del colegio de educación especial ¿María Corredentora¿ de Madrid. Se utilizan las pruebas del Test MABC para el tramo de 4 a 6 años de edad (con algunas adaptaciones) y la escala de observación ECOMI tomada como criterio de validez. Resultados y conclusiones: El módulo de 4 a 6 años del test MABC es aplicable, con ligeras modificaciones, para evaluar las habilidades motrices fundamentales de niños y niñas con síndrome de Down. El conjunto de las pruebas muestra coeficientes de fiabilidad y validez adecuados. El grado de desarrollo motor de estos niños (9 y 10 años), mediante la comparación con el baremo de MABC, es inferior al promedio de la población española de escolares de 4 a 6 años

The Reproducibility of Ultrasonographic Findings of Rectosigmoid Endometriosis Among Examiners With Different Level of Expertise

Objective: To analyze the reproducibility of ultrasonographic (US) findings of rectosigmoid endometriosis among examiners with different level of expertise using stored three-dimensional (3D) volumes of the posterior compartment of the pelvis as a part of SANABA (Sardinia-Navarra-Barcelona) collaborative study. Materials and methods: Six examiners in 3 academic Department of Obstetrics and Gynecology, with different levels of experience and blinded to each other, evaluated 60 stored 3D volumes from the posterior compartment of the pelvis and looked for the presence or absence of features of rectosigmoid endometriotic lesions defined as an irregular hypoechoic nodule with or without hypoechoic foci at the level of the muscularis propria of the anterior wall rectum sigma. Multiplanar view and virtual navigation were used. All examiners had to assess the 3D volume of posterior compartment of the pelvis and classify it as present or absent disease. To analyze intra-observer and the inter-observer agreements, each examiner performed the assessment twice with a 2-week interval between the first and second assessments. Reproducibility was assessed by calculating the weighted Kappa index. Results: Intra-observer reproducibility was moderate to very good for all observers (Kappa index ranging from 0.49 to 0.96) associated with a good diagnostic accuracy of each reader. Inter-observer reproducibility was fair to very good (Kappa index range: 0.21–0.87). Conclusions: The typical US sign of rectosigmoid endometriosis is reasonably recognizable to observers with different level of expertise when assessed in stored 3D volumes

Ultrasonography and atypical sites of endometriosis

In the present pictorial we show the ultrasonographic appearances of endometriosis in atypical sites. Scar endometriosis may present as a hypoechoic solid nodule with hyperechoic spots while umbilical endometriosis may appear as solid or partially cystic areas with ill-defined margins. In the case of endometriosis of the rectus muscle, ultrasonography usually demonstrates a heterogeneous hypoechogenic formation with indistinct edges. Inguinal endometriosis is quite variable in its ultrasonographic presentation showing a completely solid mass or a mixed solid and cystic mass. The typical ultrasonographic finding associated with perineal endometriosis is the presence of a solid lesion near to the episiotomy scar. Under ultrasonography, appendiceal endometriosis is characterized by a solid lesion in the wall of the small bowel, usually well defined. Superficial hepatic endometriosis is characterized by a small hypoechoic lesion interrupting the hepatic capsula, usually hyperechoic. Ultrasound endometriosis of the pancreas is characterized by a small hypoechoic lesion while endometriosis of the kidney is characterized by a hyperechoic small nodule. Diaphragmatic endometriosis showed typically small hypoechoic lesions. Only peripheral nerves can be investigated using ultrasound, with a typical solid appearance. In conclusion, ultrasonography seems to have a fundamental role in the majority of endometriosis cases in "atypical" sites, in all the cases where "typical" clinical findings are present

La percepción que los corredores kenianos tienen de sus actividades entrenamiento

El presente estudio se enmarca dentro de la Teoría del RendimientoExperto. Esta teoría propone que para llegar a ser experto en undominio, un sujeto debe superar un periodo de adquisición extensivo consistenteen miles de horas de práctica intencionalmente diseñada para mejorar.El presente estudio buscó analizar las percepciones subjetivas de un grupode corredores kenianos de larga distancia sobre sus tareas de entrenamientopara lo cual cumplimentaron un cuestionario basado en una taxonomía deactividades de entrenamiento valoradas en cuatro dimensiones: Relevancia,Esfuerzo, Concentración y Diversión. En este estudio participaron 27 corredoresde fondo kenianos divididos en tres grupos de niveles por su marca.El rango de edades de los participantes fue de 21 a 39 años (M= 25,39; DT=3,82). Todos estos corredores eran especialistas de las pruebas de media maratóny maratón. Fueron divididos en tres grupos de nivel de rendimientopor su marca: Medio, Alto y Muy Alto. Los resultados mostraron comolas dimensiones de Concentración, Esfuerzo y Disfrute diferenciaron a loscorredores por su nivel, asímismo se manifestó el papel que las actividadesgrupales de entrenamiento tienen para estos corredores, lo que plantea lacuestiòn si los modelos de desarrollo de la excelencia desarrollados en enlos paises desarrollados sirven para explicar este fenómeno en los países envías de desarrollo