Las relaciones de convivencia de los niños, niñas y adolescentes sordos o hipoacústicos: estudio cualitativo exploratorio

Estudio cualitativo exploratorio con enfoque fenomenológico que estudió en 10 Niños, Niñas y Adolescentes Sordos / HipoAcústicos (NNA-S/HA) las relaciones de convivencia con la familia, los profesionales de salud, los maestros, los amigos, la comunidad sorda; las cualidades de resiliencia de los NNA-S/HA encontró que las madres aunque tienen altos niveles de estrés son las que afrontan las dificultades y apoyan la intervención, los NNA-S/HA se refugian en sus madres; y los padres se retraen en sus sentimientos y evaden los problemas, y por eso abandonan el hogar al enterarse de que su hijo es sordo. Los profesionales carecen de estrategias para la atención y la comunicación, son distantes del NNA-S/HA, las familias relatan mala calidad en los servicios de salud. Los maestros y los amigos de los NNA-S/HA que van escuelas regulares les excluyen causando convivencias desagradables para los NNA-S/HA. Aquellos que se encuentran en la escuela para sordos se sienten más adaptados, con mejor autoestima y son más resiliente. La mitad de los NNA-S/HA usan dispositivos auditivos pero todos usan o lengua de señas formal o señas familiares para comunicarse con sus amigos y familias. Los NNA-S/HA que usan los dispositivos auditivos no tienen contacto con la comunidad sorda de su región no así los otros que no lo usan y cuya lengua principal es la de señas. Los NNA-S/HA desarrollan como todos los demás sueños, proyectos de vida y luchan por conseguirlo. El estudio permite plantear hipótesis para futuras investigaciones en torno a las estrategias de afrontamiento de las familias, la resiliencia de los NNA-S/HA y la asociación con las relaciones de convivencia

The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma

The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

[Rationale]: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer.[Objectives]: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC.[Methods]: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples.[Measurements and Main Results]: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer.[Conclusions]: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy.Supported by Fundación para la Investigación Médica Aplicada (FIMA), Spanish Ministry of Economy and Innovation and Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional grants 12/02040, PI13/00806, PI16/01821, PI16/00280, RTICC RD12/0036/0040, and SAF2015-6455-R; Centro de Investigación Biomédica en Red de Cáncer grants CB16/12/00390, CB16/12/00390, CB16/12/00442, and CB16/12/00443; Asociación Española Contra el Cáncer (AECC) Scientific Foundation grant GCB14-2170; Bristol-Myers Squibb (preclinical research agreement); AECC and a fellowship from the Basque Government (I.G.); the Castilla-León Government grant CSI049 U16 , the Ministry of Economy and Competitiveness grant SAF2015-64556-R , the Fundación Ramón Areces, Worldwide Cancer Research grant 14-1248 , and AECC Scientific Foundation grant GC16173472GARC (X.R.B.); and the Spanish Ministry of Science, Innovation and Universities (MCIU, RTI 2018-094507-B-100), La Caixa Foundation and Caja Navarra Foundation (F.L.).Peer reviewe