RESUMO
OBJECTIVES: Online patient forums have become a platform for patient education and advocacy in many areas of medicine. The anonymity provided by such forums may encourage honest, candid responses. Using patient online reviews, this study sought to explore themes that arose from negatively perceived care interactions with American otolaryngologists using the Accreditation Council for Graduate Medical Education (ACGME) competency framework. STUDY DESIGN: Qualitative thematic analysis. METHODS: Through an iterative multistep process, a qualitative thematic analysis was conducted on negative reviews (defined as ratings of two or less out of five) of all American otolaryngologists found on a popular online physician-rating website (RateMDs.com). RESULTS: A systematic search through the RateMDs website revealed 2950 separate comments of negative reviews. Of these negative reviews, 350 were randomly selected for thematic analysis. The predominant themes that emerged aligned closely with the Accreditation Council for Graduate Medical Education (ACGME) competencies, in particularly with professionalism and interprofessional skills and communication. CONCLUSIONS: The negative reviews of American otolaryngologists revealed a number of areas where improvements could be made to quality of care. Patients value evidence-based medicine delivered by compassionate and respectful physicians. Isolating and aligning predominant themes within the ACGME framework proved a productive method to collect and organize pertinent patient feedback and integrate teaching into the post-graduate training and continuing professional development in order to avoid such negatively perceived interactions in the future.
RESUMO
Angiopoietin 1 (Ang1) is an activating ligand for the endothelial receptor tyrosine kinase Tie2, whereas Ang2 acts as a context-dependent agonist or antagonist that has a destabilizing effect on the vasculature. The molecular mechanisms responsible for the versatile functions of Ang2 are poorly understood. We show here that Ang2, but not Ang1, induces Tie2 translocation to the specific cell-matrix contact sites located at the distal end of focal adhesions. The Ang2-specific Tie2 translocation was associated with distinct Tie2 activation and downstream signals which differed from those of Ang1, and led to impaired cell motility and weak cell-matrix adhesion. We demonstrate that the different oligomeric or multimeric forms of the angiopoietins induce distinct patterns of Tie2 trafficking; the lower oligomerization state of native Ang2 was crucial for the Ang2-specific Tie2 redistribution, whereas multimeric structures of Ang1 and Ang2 induced similar responses. The Ang2-specific Tie2 trafficking to cell-matrix contacts was also dependent on the cell substratum, α2ß1-integrin-containing cell-matrix adhesion sites and intact microtubules. Our data indicate that the different subcellular trafficking of Tie2-Ang2 and Tie2-Ang1 complexes generates ligand-specific responses in the angiopoietin-Tie signaling pathway, including modulation of cell-matrix interactions.
Assuntos
Angiopoietina-1/química , Angiopoietina-2/química , Endotélio Vascular/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Corpo Vítreo/irrigação sanguínea , Angiopoietina-1/genética , Angiopoietina-1/farmacologia , Angiopoietina-2/genética , Angiopoietina-2/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Junções Célula-Matriz/efeitos dos fármacos , Junções Célula-Matriz/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Injeções Intravítreas , Camundongos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Células NIH 3T3 , Neovascularização Fisiológica , Multimerização Proteica , Receptores Proteína Tirosina Quinases/genética , Receptor TIE-2 , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Solid tumors require blood vessels for growth and dissemination, and lymphatic vessels as additional conduits for metastatic spread. The identification of growth factor receptor pathways regulating angiogenesis has led to the clinical approval of the first antiangiogenic molecules targeted against the vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-2 pathway. However, in many cases resistance to anti-VEGF-VEGFR therapy occurs, and thus far the clinical benefit has been limited to only modest improvements in overall survival. Therefore, novel treatment modalities are required. Here, we discuss the members of the VEGF-VEGFR family as well as the angiopoietin growth factors and their Tie receptors as potential novel targets for antiangiogenic and antilymphangiogenic therapies.
