RESUMEN
Poorly differentiated (PD) chordoma, a rare, aggressive tumor originating from notochordal tissue, shows loss of SMARCB1 expression, a core component of the Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. To determine the impact of SMARCB1 re-expression on cell growth and gene expression, two SMARCB1-negative PD chordoma cell lines with an inducible SMARCB1 expression system were generated. After 72 hours of induction of SMARCB1, both SMARCB1-negative PD chordoma cell lines continued to proliferate. This result contrasted with those observed with SMARCB1-negative rhabdoid cell lines in which SMARCB1 re-expression caused the rapid inhibition of growth. We found that the lack of growth inhibition may arise from the loss of CDKN2A (p16INK4A) expression in PD chordoma cell lines. RNA-sequencing of cell lines after SMARCB1 re-expression showed a down-regulation for rRNA and RNA processing as well as metabolic processing and increased expression of genes involved in cell adhesion, cell migration, and development. Taken together, these data establish that SMARCB1 re-expression in PD chordomas alters the repertoire of SWI/SNF complexes, perhaps restoring those associated with cellular differentiation. These novel findings support a model in which SMARCB1 inactivation blocks the conversion of growth-promoting SWI/SNF complexes to differentiation-inducing ones, and they implicate SMARCB1 loss as a late event in tumorigenic progression. Importantly, the absence of growth inhibition after SMARCB1 restoration creates a unique opportunity to identify therapeutic vulnerabilities.
Asunto(s)
Cordoma , Humanos , Cordoma/genética , Cordoma/patología , Factores de Transcripción/metabolismo , Diferenciación Celular/genética , Carcinogénesis , Proteína SMARCB1/genéticaRESUMEN
PURPOSE: Emergency departments (EDs) care for patients with complex medical problems who require a coordinated care approach. Patient navigation services, which help assist patients with care coordination, have been widely implemented for patients with cancer in a variety of settings, but this approach has not been described in the ED. We sought to better understand the potential for ED-based patient navigation services from the perspective of individuals currently providing these services in other settings. METHODS: A survey was conducted of participants at a regional conference for patient navigation services of patients with cancer. RESULTS: Eighty-five completed surveys were returned representing a response rate of 64%. Ninety-one percent of responses indicated that lay navigation services would be either very helpful or moderately helpful for either ED patients with cancer or for ED patients aged 65 years or older with or without cancer in an ED. Coordination of care, the provision of emotional support and educational resources relevant to their medical conditions, and providing companionship to older patients during the ED visits were identified as priorities for an ED-based lay navigation program. The lack of navigators with experience in the ED, the physical space constraints of the ED, and the time constraints associated with an ED visit were identified as the primary barriers to establishing a lay navigation program in the ED. CONCLUSIONS: These results identify the care priorities and barriers to be overcome during the development of an ED-based lay navigation program from the perspective of those currently providing patient navigator services.