Prostate tumor OVerexpressed-1 (PTOV1) down-regulates HES1 and HEY1 notch targets genes and promotes prostate cancer progression

Background PTOV1 is an adaptor protein with functions in diverse processes, including gene transcription and protein translation, whose overexpression is associated with a higher proliferation index and tumor grade in prostate cancer (PC) and other neoplasms. Here we report its interaction with the Notch pathway and its involvement in PC progression. Methods Stable PTOV1 knockdown or overexpression were performed by lentiviral transduction. Protein interactions were analyzed by co-immunoprecipitation, pull-down and/or immunofluorescence. Endogenous gene expression was analyzed by real time RT-PCR and/or Western blotting. Exogenous promoter activities were studied by luciferase assays. Gene promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP). In vivo studies were performed in the Drosophila melanogaster wing, the SCID-Beige mouse model, and human prostate cancer tissues and metastasis. The Excel package was used for statistical analysis [...]

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans¿ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome

Cobertura de grandes quemados con cultivo de queratinocitos: casuística de nuestra Unidad y protocolo de tratamiento Massive burn coverage with keratinocytes cultured: our casuistry and treatment protocol

El paciente gran quemado sigue siendo hoy en día un difícil reto al que se enfrentan múltiples profesionales sanitarios. La elevada mortalidad de estos pacientes se justifica por la severa alteración del estado general que sufren, las múltiples complicaciones que se asocian y por la ausencia de piel válida para cubrir las quemaduras, como sucede en el caso de los quemados de gran extensión. Este último inconveniente se solventa de diferentes maneras, siendo una de las más importantes el cultivo de queratinocitos. En la Unidad de Quemados del Hospital Universitario de Cruces en Baracaldo (Vizcaya), España, iniciamos la aplicación de esta técnica en 2001, con una experiencia acumulada en esta década de 14 pacientes. El objetivo de este artículo es mostrar nuestro protocolo de aplicación del procedimiento para la cobertura de quemados extensos, los criterios de inclusión y la terapéutica pre y postaplicación de las láminas de queratinocitos que empleamos en nuestra Unidad. Así mismo, presentamos las características de los pacientes tratados y nuestra propia experiencia en la aplicación de esta técnica que, a pesar de lograr resultados cada vez más satisfactorios y ser en ocasiones la única alternativa para un paciente extensamente quemado, tiene todavía hoy en día tantos detractores.<br>The severe burn patient continues being nowadays a difficult challenge which multiple sanitary professionals face. The high mortality of these patients justifies itself by the severe alteration of the general condition, the multiple complications that they suffer and the absence of skin for their coverage, as is the case of extensive burns. This last disadvantage is settled in different ways, being one of the most important the treatment with keratinocytes culture. In the Cruces Universitary Hospital Burn Unit in Baracaldo (Vizcaya), Spain, we began the clinical application of this technique in 2001, with a 14 patients accumulated experience in this period of time. The aim of this article is to show our treatment protocol for the coverage of massive burns, the inclusion criteria and the therapeutics pre and postapplication of keratinocytes. Likewise, we expose the characteristics of the treated patients and our own experience in the application of this technique that, although achieving increasingly satisfactory results, even being sometimes the unique alternative for severe burn patients, still has nowadays many detractors

Colgajo de perforantes de la arteria colateral cubital inferior para defectos por quemadura eléctrica en fosa cubital

Las quemaduras eléctricas producen lesiones profundas, especialmente las debidas a la entrada y salida de la corriente y al arco voltaico, que pueden dejar expuestas estructuras nobles y afectar áreas de flexo-extensión, como la fosa antecubital. Los defectos resultantes pueden cubrirse mediante colgajos libres o pediculados de brazo y antebrazo. Entre las distintas opciones quirúrgicas, el colgajo medial del brazo evita la interrupción de los ejes vasculares mayores y la secuela en la zona donante es discreta. Sin embargo, su uso está poco extendido por considerarse un colgajo de difícil disección debido a la variabilidad anatómica de las arterias colaterales cubitales superior e inferior que lo irrigan. Presentamos la cobertura para un defecto secundario a quemadura eléctrica en la fosa antecubital mediante un colgajo medial del brazo basado en las ramas perforantes de la arteria colateral cubital inferior. Aunque confirmamos en este caso la variabilidad vascular, la disección resultó sencilla y el resultado estético y funcional fue excelente