RESUMEN
PURPOSE: In this work we examined the presence of the neural stem cell biomarker Hairy and Enhancer of Split 3 (Hes3) in the anterior eye segment and in the aberrant growth condition of the conjunctiva pterygium. Further, we studied the response of Hes3 to irradiation. MATERIALS AND METHODS: Adult mouse and human corneoscleral junction and conjunctiva, as well as human pterygium were prepared for immunohistochemical detection of Hes3 and other markers. Total body irradiation was used to study the changes in the pattern of Hes3 expression. RESULTS: The adult rodent and human eye as well as pterygium, contain a population of cells expressing Hes3. In the human eye, Hes3-expressing (Hes3+) cells are found predominantly in the subconjunctival space spanning over the limbus where they physically associate with blood vessels. The cytoarchitecture of Hes3 + cells is similar to those previously observed in the adult central nervous system. Furthermore, irradiation reduces the number of Hes3 + cells in the subconjunctival space. In contrast, irradiation strongly promotes the nuclear localization of Hes3 in the ciliary body epithelium. CONCLUSIONS: Our results suggest that a recently identified signal transduction pathway that regulates neural stem cells and glioblastoma cancer stem cells also operates in the ocular surface, ciliary body, and in pterygium.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Unión al ADN/metabolismo , Ojo/metabolismo , Regulación de la Expresión Génica , Proteínas del Tejido Nervioso/metabolismo , Pterigion/metabolismo , Factores de Transcripción/metabolismo , Animales , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Conjuntiva/efectos de la radiación , Ojo/irrigación sanguínea , Ojo/efectos de los fármacos , Ojo/efectos de la radiación , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Ratones , Terapia Molecular Dirigida , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/efectos de la radiación , Pterigion/tratamiento farmacológico , Pterigion/fisiopatología , Proteínas RepresorasRESUMEN
Tumors exhibit complex organization and contain a variety of cell populations. The realization that the regenerative properties of a tumor may be largely confined to a cell subpopulation (cancer stem cell) is driving a new era of anti-cancer research. Cancer stem cells from Glioblastoma Multiforme tumors express markers that are also expressed in non-cancerous neural stem cells, including nestin and Sox2. We previously showed that the transcription factor Hes3 is a marker of neural stem cells, and that its expression is inhibited by JAK activity. Here we show that Hes3 is also expressed in cultures from glioblastoma multiforme which express neural stem cell markers, can differentiate into neurons and glia, and can recapitulate the tumor of origin when transplanted into immunocompromised mice. Similar to observations in neural stem cells, JAK inhibits Hes3 expression. Hes3 RNA interference reduces the number of cultured glioblastoma cells suggesting a novel therapeutic strategy.
Asunto(s)
Neoplasias del Sistema Nervioso Central/patología , Proteínas de Unión al ADN/metabolismo , Glioblastoma/patología , Células Madre Neoplásicas/metabolismo , Factores de Transcripción/metabolismo , Angiopoyetina 2/metabolismo , Animales , Biomarcadores/metabolismo , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/metabolismo , Proteínas de Unión al ADN/genética , Células Madre Embrionarias/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Janus Quinasa 1/metabolismo , Janus Quinasa 1/farmacología , Ratones , Células Madre Neoplásicas/patología , Fosforilación , ARN Interferente Pequeño , Proteínas Represoras , Factor de Transcripción STAT3/metabolismo , Factores de Transcripción/genética , Células Tumorales CultivadasRESUMEN
Adequate quality of diabetes care and the best concept for the implementation of national diabetes plans remain controversial. In September 2011 the United Nations High Level Meeting on Non Communicable Diseases agreed on a consensus that national plans for the prevention and control of diabetes should be developed, implemented and monitored. The Global Diabetes Survey (GDS) is a standardised, annual, global questionnaire that will be used to assess responses of representatives from 19 diabetes-related stakeholder groups. It was designed with the goal of generating an annual report on the quality of national diabetes care and to compare findings from different regions and countries. The findings will be freely available for everyone's use and will be used to inform politicians and stakeholders to encourage the improvement of the quality of diabetes care in its medical, economical, structural and political dimensions.