ABSTRACT
Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Drug Resistance, Neoplasm/genetics , Glioma/genetics , Glioma/metabolism , O(6)-Methylguanine-DNA Methyltransferase/genetics , O(6)-Methylguanine-DNA Methyltransferase/metabolism , Temozolomide/pharmacology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Cell Line, Tumor , Female , Glioma/diagnosis , Glioma/drug therapy , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm StagingABSTRACT
Resumen El presente artículo expone los resultados de una investigación empírica que se ha adentrado en las experiencias y discursos ciudadanos respecto del tema de la muerte en dignidad, y de la legitimidad de la implementación de medidas de acompañamiento de este proceso. A través del análisis de lo obtenido en siete grupos de discusión, llevados a cabo en la Región Metropolitana de Santiago de Chile, se ha podido concluir la existencia de altos niveles de consenso en la ciudadanía, respecto de la legitimidad de implementar medidas externas para terminar con la vida de pacientes que lo soliciten debido al padecimiento de enfermedades terminales, y de la necesidad de contar con una normativa legal que respalde su aplicación. Todo esto en el marco de una amplia valoración ciudadana de la autonomía personal y desde la narración de experiencias que revelan los grandes costos emocionales y monetarios que implica el cuidado de personas con enfermedades terminales.
Abstract This article presents the results of empirical research that investigates the citizen's perspectives regarding the issue of death with dignity and the legitimacy of the implementation of measures to accompany this process. Through the implementation and analysis of seven discussion groups, carried out in the Metropolitan Region of Santiago de Chile, it can be concluded that there are high levels of consensus among the citizens supporting the need for implementation of external measures to end the life of patients who request it due to suffering related to terminal illnesses, and the need to have legal regulations that supports its application. All of this has been evaluated within the framework of a broad citizen assessment of personal autonomy and from the narration of experiences that reveal the great emotional and monetary burden involved in the process of caring for people with terminal illnesses.
Resumo O presente artigo expõe os resultados de uma investigação empírica que adentrou as experiências e discursos cidadãos a respeito do tema da morte com dignidade e da legitimidade da implementação de medidas de acompanhamento deste processo. Através da análise do obtido em sete grupos de discussão, levados a cabo na Região Metropolitana de Santiago do Chile, se pode demonstrar a existência de altos níveis de consenso entre as pessoas no que diz respeito à legitimidade de implementar medidas externas para terminar com a vida de pacientes que as solicitem devido ao padecimento de enfermidades terminais e da necessidade de contar com uma normativa legal que respalde sua aplicação. Tudo isto no contexto de uma ampla valorização cidadã da autonomia pessoal e a partir da narrativa de experiências que revelam os grandes custos emocionais e econômicos implicados no cuidado de pessoas com enfermidades terminais.
Subject(s)
Humans , Right to Die , Community Participation , Death , Empathy , Respect , ChileABSTRACT
The aim of the present study is to check whether we can replicate, in an independent series, previous results showing that the molecular study of pituitary-specific gene expression complements the inmunohistochemical identification of pituitary neuroendocrine tumours. We selected 112 patients (51 (46.4%) women; mean age 51.4±16 years; 102 macroadenomas (91.9%), 9 microadenomas (8.1%)) with complete clinical, radiological, immunohistochemical and molecular data from our data set of pituitary neuroendocrine tumours. Patients were different from those previously studied. We measured the expression of the pituitary-specific hormone genes and type 1 corticotrophin-releasing hormone and arginine vasopressin 1b receptors, by quantitative real-time polymerase chain reaction using TaqMan probes. Afterwards, we identified the different pituitary neuroendocrine tumour subtypes following the 2017 World Health Organization classification of pituitary tumours, calculating the concordance between their molecular and immuhistochemical identification. The concordance between molecular and immunohistochemical identification of functioning pituitary neuroendocrine tumours with the clinical diagnosis was globally similar to the previous series, where the SYBR Green technique was used instead of TaqMan probes. Our results also corroborated the poor correlation between molecular and immunohistochemical detection of the silent pituitary neuroendocrine tumour variants. This discrepancy was more remarkable in lactotroph, null-cell and plurihormonal pituitary neuroendocrine tumours. In conclusion, this study validates the results previously published by our group, highlighting a complementary role for the molecular study of the pituitary-specific hormone genes in the typification of pituitary neuroendocrine tumours subtypes.
Subject(s)
Neuroendocrine Tumors/diagnosis , Pituitary Hormones/genetics , Pituitary Neoplasms/diagnosis , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Vasopressin/genetics , Adult , Aged , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Pituitary Gland/pathology , Pituitary Neoplasms/genetics , Pituitary Neoplasms/pathologyABSTRACT
BACKGROUND: The National Socioeconomic Characterization Survey (CASEN) was modified in the year 2000, to include an assessment of the inequalities in the access to health services. AIM: To analyze the health issues of year 2000 survey database. MATERIAL AND METHODS: During 2000, 38338 urban and 26698 rural dwellings were surveyed, totaling 240000 people analyzing ascription to public or private health services and the need demand and use of these services. RESULTS: A higher risk population (lower income, higher age and women) is ascribed to public health services. Sixty five percent of the population self perceives their health as good, this figure decreases along with age and women have a worse self perception than men. In the 30 days prior to the survey, 13% of the population had a health related event; this figure was higher among women and the lower income quintiles. Expressed health demand was higher among women and lower income quintiles. A multivariate analysis identified an age below 14 years, pertaining to a minority ethnic group, ascription to private health services, residing in rural areas, pertaining to the lower income quintile and male sex, as factors associated to a lack access to health care. In the adjusted model, pertaining to the National Health Fund (a public system) is a protective factor to receive health services. CONCLUSIONS: The significant inequalities in the access to health care should be corrected with the new Health Reform. The new module incorporated to the National Socioeconomic Characterization Survey, is useful to assess the access to health care in Chile.
